The contradictory effect of macrophage-related cytokine expression in lumbar disc herniations: a systematic review.
Djuric N,Lafeber G C M,Vleggeert-Lankamp C L A
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
PURPOSE:Sciatic symptoms due to lumbar disc herniation are likely to be caused not solely by mechanical compression of the nerve root, but also by pain-inducing elements from inflammatory processes. Key components in the inflammatory reaction are M1 and M2 macrophages, with the M1 type being associated with pro-inflammatory processes and M2 with anti-inflammatory-processes. METHOD:The present systematic review summarizes all studies on associations between M1 and M2 macrophages and their related inflammation factors and pain symptoms in lumbar disc herniations. Literature search was performed using an optimally sensitive search string. Studies were selected for inclusion by means of predefined inclusion and exclusion criteria and subsequently graded for risk of bias. A total of 14 studies were included. Overall risk of bias was moderate (8/14), and three studies had high risk of bias and three has low risk of bias. RESULTS:Regarding M1-related cytokines, high levels of TNF-α, TNFR1, IL-6, IL-8, and IFN-γ were all associated high VAS scores. In contrast, high levels of TNFR2 were associated with lower VAS scores. Moreover, no associations were found for IL-1a and IL-1β. Results regarding M2-related cytokines revealed the opposite: high levels of both IL-4 and IL-10 were associated with lower VAS scores. No associations were established for TGF-β. Moreover, the presence of macrophages (CD68) was negatively associated with VAS scores. CONCLUSION:While M1-related pro-inflammatory cytokines worsen pain symptoms, M2-related anti-inflammatory cytokines alleviate pain symptoms. Nevertheless, the present evidence is limited, and further research on the underlying pathophysiological mechanism in sciatica is required. These slides can be retrieved under Electronic Supplementary Material.
10.1007/s00586-019-06220-w
[Function, molecular structure and gene expression of IL-8].
Okamoto S,Nomura H,Matsushima K
Nihon rinsho. Japanese journal of clinical medicine
Interleukin-8 (IL-8) is a potent chemotactic factor for neutrophils and T lymphocytes. Various reagents such as lectins, mitogens, IL-1, TNF, induce IL-8 production in a wide range of cells and tissues. The IL-8 gene is known to be activated by AP-1, NF-kB like factor and C/EBP like factor, but the relative importance of these transcriptional factors varies from cell to cell. Two types of human IL-8 receptor cDNA have recently been cloned. Both are G-protein coupled receptors and the amino acid sequences are highly homologous. Other members of the IL-8 family, such as GRO/MGSA and MIP2, bind to IL-8 receptors, and the receptors of other chemoattractants such as fMLP and C5a, show high homology to the IL-8 receptors.
Essential involvement of interleukin-8 (IL-8) in acute inflammation.
Harada A,Sekido N,Akahoshi T,Wada T,Mukaida N,Matsushima K
Journal of leukocyte biology
Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as neutrophil infiltration in these conditions. These results suggest that IL-8 plays a causative role in acute inflammation by recruiting and activating neutrophils.
Some aspects of IL-8 pathophysiology. III: Chemokine interaction with endothelial cells.
Rot A,Hub E,Middleton J,Pons F,Rabeck C,Thierer K,Wintle J,Wolff B,Zsak M,Dukor P
Journal of leukocyte biology
Chemokines have been convincingly implicated in driving leukocyte emigration in different inflammatory reactions. However, the cellular and molecular mechanisms of chemokine involvement in leukocyte emigration are not clear. We and others suggested that leukocyte adhesion to the endothelium and transmigration are induced by chemokines immobilized on the endothelial cell surface. This would require the presence of specific chemokine binding sites in this microanatomical location. Using an in situ binding assay we demonstrated the presence of binding sites for interleukin-8 (IL-8) and RANTES, but not monocyte inflammatory protein-1 alpha on the endothelium of postcapillary venules and small veins in human skin. In contrast, venules and veins in various anatomical locations showed dramatically differing IL-8 binding patterns. The subcellular distribution of IL-8 in the venular endothelial cells following its in vivo and ex vivo injections was studied by use of electron microscopy. Our results suggest that IL-8 was internalized by the endothelial cells, transported transcellularly via plasmalemmal vesicles, and released onto the luminal surface where it appeared located preferentially on tips of membrane protrusions. We were unable to study the endothelial IL-8 binding or transport in vitro because all the in vitro propagated endothelial cell lines and primary endothelial cells tested lacked IL-8 binding sites. This includes human umbilical vein endothelial cells (HUVECs), which also did not bind IL-8 in situ. However, HUVECs provided a satisfactory in vitro system to study the secretion of IL-8 by the endothelial cells. Two possible alternative pathways were described: secretion directly from the Golgi apparatus or following storage in Weibel-Palade bodies.
10.1002/jlb.59.1.39
Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions.
Mukaida N,Harada A,Matsushima K
Cytokine & growth factor reviews
Leukocyte infiltration is a hallmark of inflammation. Knowledge on molecular mechanisms of leukocyte infiltration has advanced rapidly due to the recent elucidation of structures and functions of adhesion molecules and chemokines. Since the discovery of interleukin-8 (IL-8), a prototype of CXC chemokines, in 1987 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), a prototype of chemotactic cytokines (CC) chemokines, in 1989, more than 30 members of chemokines have been identified so far. Evidence is accumulating that these chemokines exert overlapping but distinct actions on specific types of leukocytes in vitro through interacting with their specific G-protein-coupled receptors with seven transmembrane domains. However, redundancy at receptor levels has frequently hindered the clarification on the precise physiological or pathophysiological roles of chemokines. Here, we describe the pathophysiological roles of IL-8 and MCAF/MCP-1 in several animal models of neutrophil- and macrophage-mediated inflammation, respectively, by focusing on our recent work using neutralizing antibodies to these chemokines. We discuss further potential roles of these chemokines in T-lymphocyte-mediated immune responses.
10.1016/s1359-6101(97)00022-1
Oxidant stress regulation of IL-8 and ICAM-1 gene expression: differential activation and binding of the transcription factors AP-1 and NF-kappaB (Review).
Roebuck K A
International journal of molecular medicine
Reactive oxygen species (ROS), generated either extracellularly or intracellularly through ligand-receptor interactions, can function as signal transduction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (ICAM-1; CD54). Together, IL-8 and ICAM-1 orchestrate the transendothelial migration of neutrophils to sites of inflammation and injury. Recent results demonstrate that oxidant stress generated directly by exogenous H2O2 differentially induce IL-8 and ICAM-1 transcription in epithelial and endothelial cells. H2O2 induces IL-8 but not ICAM-1 in the A549 type-II-like epithelial cell line, whereas in a microvessel endothelial cell line (HMEC-1) as well as in primary endothelial cells, H2O2 induces ICAM-1 but not IL-8, which is spontaneously expressed. In contrast, the pro-inflammatory cytokine TNFalpha, whose activity is dependent on the generation of intracellular ROS, induces IL-8 and ICAM-1 in both cell types. The differential induction of IL-8 and ICAM-1 by H2O2 and TNFalpha suggest that the two inflammatory stimuli target distinct redox responsive signaling pathways to activate cell type-specific gene expression. In this regard, we found that the cell type-specific pattern of IL-8 and ICAM-1 gene expression was associated with the differential activation and promoter binding of the redox regulated transcription factors AP-1 and NF-kappaB. In this review, our current understanding of the redox regulation of the IL-8 and ICAM-1 genes is summarized, and the differential roles AP-1 and NF-kappaB play in their cell type-specific expression, with particular emphasis on the differential effects induced by TNFalpha and H2O2 is discussed.
10.3892/ijmm.4.3.223
Interleukin 8 (IL-8) and the release of leukocytes from the bone marrow.
van Eeden S F,Terashima T
Leukemia & lymphoma
Interleukin 8 (IL-8) is produced by various cells upon stimulation and influences a variety of functions of leukocytes in particular neutrophils. Systemic administration of IL-8 induces a rapid neutropenia associated by sequestration of neutrophils in the lung that is followed by a neutrophilia characterized by the rapid release of neutrophils from the bone marrow. These cells are released predominantly from the bone marrow venous sinusoids. In addition, several studies have shown the potential role of IL-8 in hematopoiesis and trafficking of hematopoietic stem cells. Systemic administration of IL-8 induces a rapid mobilization of progenitors from the bone marrow with long-term myelo-lymphoid repopulation capacity. It has been employed clinically to mobilize hematopoietic progenitor cells into the peripheral blood and used for autologous or allogeneic bone marrow transplantation. The mechanism for these effects of IL-8 is largely speculative. This report summarizes current ideas on the possible mechanisms how IL-8 influences cell trafficking in and from the bone marrow.
10.3109/10428190009089427
[The study on the interleukin-8 (IL-8)].
Zhang Wensheng,Chen Huaiqing
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi
Interleukin-8 (IL-8), which is a member of C-X-C chemokine subfamily, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. Numerous reports show that various cells express IL-8 mRNA and produce IL-8 protein rapidly, including monocytes, T lymphocytes, neutrophils, fibroblasts, endothelial cells and epithelial cells. The human IL-8 gene has a length of 5191 bp and contains four exons separated by three introns. It maps to human chromosome 4q12-q21. The mRNA consists of a 101 bases 5' untranslated region, an open reading frame of 297 bases, and a long 3' untranslated region of 1.2 kb. The 5' flanking region of the IL-8 gene contains potential binding sites for several nuclear factors including activated protein-1 (AP-1), activated protein-2 (AP-2), nuclear factor-gene binding (NF-kappa B), nuclear factor-interleukin-6 (NF-IL-6, also calls CAAT/enhancer-binding proteins, C/EBP), IFN regulatory factor-1 (IRF-1), hepatocyte nuclear factor-1 (HNF-1), and so on. IL-8 gene expression is regulated initially at the level of gene transcription. The rapid induction of IL-8 gene expression is likely mediated by latent transcription factors that bind the IL-8 promoter. AP-1 and NF-IL-6 physically interact with NF-kappa B, and functional cooperativity among these factors appears to be critical for optimal IL-8 promoter activity in different cell types. The IL-8 receptor (IL-8R) is a dimeric glycoprotein consisting of a 59 KDa and a 67 KDa subunit. It has been given the name CDw128. It is expressed in many different cell types including those not responding to IL-8. The receptor density is approximately 20,000/cell in neutrophils, 1,040/cell in monocytes, and 300/cell in T-lymphocytes. The IL-8R is a member of the family of G-protein-coupled receptors. There are at least two different IL-8 receptor types (CXCR1 and CXCR2). The activities of IL-8 are not species-specific. IL-8 affects the adhesion of neutrophils to the endothelium and induces the transendothelial migration of neutrophils. IL-8 also exhibits in vitro chemotactic activities against of T-lymphocytes and basophils. IL-8 gene expression can be regulated by fluid shear stress, which may play an important role in the genesis and development of both inflammation and arterosclerosis.
The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15.
Nielsen Anders Rinnov,Pedersen Bente Klarlund
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle-fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.
10.1139/H07-054
The functional significance behind expressing two IL-8 receptor types on PMN.
Stillie RoseMarie,Farooq Shukkur Muhammed,Gordon John R,Stadnyk Andrew W
Journal of leukocyte biology
PMN are critical to innate immunity and are fundamental to antibacterial defense. To localize to sites of infection, PMN possess receptors that detect chemoattractant stimuli elicited at the site, such as chemokines, complement split products, or bioactive lipids. Signaling through these receptors stimulates chemotaxis toward the site of infection but also activates a number of biochemical processes, with the result that PMN kill invading bacteria. PMN possess two receptors, CXCR1 and CXCR2, for the N-terminal ELR motif-containing CXC chemokines, although only two chemokine members bind both receptors and the remainder binding only CXCR2. This peculiar pattern in receptor specificity has drawn considerable interest and investigation into whether signaling through each receptor might impart unique properties on the PMN. Indeed, at first glance, CXCR1 and CXCR2 appear to be functionally redundant; however, there are differences. Considering these proinflammatory activities of activating PMN through chemokine receptors, there has been great interest in the possibility that blocking CXCR1 and CXCR2 on PMN will provide a therapeutic benefit. The literature examining CXCR1 and CXCR2 in PMN function during human and modeled diseases will be reviewed, asking whether the functional differences can be perceived based on alterations in the role PMN play in these processes.
10.1189/jlb.0208125
Role of CCR2 and IL-8 in acute lung injury: a new mechanism and therapeutic target.
Shen Yao,Wang Diane,Wang Xiangdong
Expert review of respiratory medicine
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases associated with very high mortality, and are the most common and earliest organ dysfunctions in the development of multiple organ dysfunction syndrome. The NIH estimates that more than 4.5 million people suffer from ALI/ARDS per year. Although the American-European Consensus Conference definition has been widely used for approximately 40 years, it still has some limitations that may impact on the conduct of clinical research and management of patients with ALI/ARDS. This article will focus on the role of CC chemokine receptor 2 and IL-8 in the pathogenesis and resolution in ALI/ARDS.
10.1586/ers.10.80
Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression.
Fousek Kristen,Horn Lucas A,Palena Claudia
Pharmacology & therapeutics
Tumor progression relies on the ability of cancer cells to effectively invade surrounding tissues and propagate. Among the many mechanisms that contribute to tumor progression is the epithelial-to-mesenchymal transition (EMT), a phenotypic plasticity phenomenon that increases the cancer cells' motility and invasiveness and influences their surrounding microenvironment by promoting the secretion of a variety of soluble factors. One such factor is IL-8, a chemokine with multiple pro-tumorigenic roles within the tumor microenvironment (TME), including stimulating proliferation or transformation of tumor cells into a migratory or mesenchymal phenotype. Further, IL-8 can increase tumor angiogenesis or recruit larger numbers of immunosuppressive cells to the tumor. Prognostically, observations in many tumor types show that patients with higher levels of IL-8 at baseline experience worse clinical outcomes. Additionally, studies have shown that the chemokine directly contributes to the development of resistance to both chemotherapy and molecularly targeted agents. More recently, clinical studies evaluating levels of IL-8 in patients receiving immune checkpoint inhibition (ICI) therapy deduced that myeloid tumor infiltration driven by IL-8 contributes to resistance to ICI agents and that peripheral IL-8 can predict outcomes to ICI therapy. Further, pre-clinical data demonstrate that targeting IL-8 or its receptors enables improved tumor killing by immune cells, and treatment strategies combining blockade of the IL-8/IL-8R axis with ICI ultimately improve anti-tumor efficacy. Based on these results and the prognostic capacity of IL-8, there are a number of ongoing clinical trials evaluating the addition of IL-8 targeting strategies to immune-based therapies.
10.1016/j.pharmthera.2020.107692
Interleukin 8 and cardiovascular disease.
Apostolakis Stavros,Vogiatzi Konstantina,Amanatidou Virginia,Spandidos Demetrios A
Cardiovascular research
Since the establishment of the inflammatory basis of atherosclerosis, several pro- or anti-inflammatory agents have been examined as potential mediators of the biochemical pathways of lesion formation. Interleukin (IL)-8 was first characterized in 1987. Since then, knowledge regarding its role in leucocyte trafficking and activation has advanced rapidly, especially in the field of cardiovascular disease. In the scientific literature, there is sufficient evidence to support beyond any doubt the involvement of IL-8 in the establishment and preservation of the inflammatory micro-environment of the insulted vascular wall. However, how the information derived from in vitro studies and animal models can be applied in clinical practice has yet to be determined. In the present review, the available evidence regarding the role of IL-8 in cardiovascular disease is presented, and future perspectives are discussed.
10.1093/cvr/cvp241
[THE ROLE OF INTERLEUKIN 8 / CXCL8 IN THE IMMUNOPATHOGENESIS AND CARCINOGENESIS OF INFLAMMATORY BOWEL DISEASES (REVIEW)].
Doszhan A,Bektayeva R,Imanbayeva N,Galiyeva A,Kurmankina A
Georgian medical news
The aim of this review was to analyze and synthesize recent data on the role of interleukin 8/CXCL8 in key mechanisms of the inflammatory process and carcinogenesis in patients with inflammatory bowel disease (IBD). Currently, the study of the relationship between the pathogenesis of cancer and chronic inflammation remains an urgent task for many researchers. It has been proven that the strongest correlation between the duration of inflammation and oncogenesis is observed in colorectal cancer (CRC). The discovery of interleukin 8 / CXCL8 as one of the powerful mediators of inflammation has expanded the general understanding of its contribution to the pathogenesis of IBD. This review emphasizes the role of CXCL8 in carcinogenesis in IBD, presents the results of studies on the molecular mechanisms of CXCL8 expression in IBD and CRC, and describes its properties as one of the main angiogenic and pro-inflammatory factors that regulate the cancer cells proliferation. Study of the effects of CXCL8 on signaling pathways activation may serve as a prerequisite for the search for and discovery of new therapeutic approaches, that will reduce the risk of CRC in patients with IBD.
Decoy oligodeoxyribonucleotides and peptide nucleic acids-DNA chimeras targeting nuclear factor kappa-B: inhibition of IL-8 gene expression in cystic fibrosis cells infected with Pseudomonas aeruginosa.
Gambari Roberto,Borgatti Monica,Bezzerri Valentino,Nicolis Elena,Lampronti Ilaria,Dechecchi Maria Cristina,Mancini Irene,Tamanini Anna,Cabrini Giulio
Biochemical pharmacology
Cystic fibrosis (CF) is characterized by a deep inflammatory process, with production and release of cytokines and chemokines, among which interleukin 8 (IL-8) represents one of the most important. Accordingly, there is a growing interest in developing therapies against IL-8, with the aim of reducing the excessive inflammatory response in the airways of CF patients. Since transcription factor NF-kappaB plays a critical role in IL-8 expression, the transcription factor decoy (TFD) strategy might be of interest. TFD is based on biomolecules mimicking the target sites of transcription factors (TFs) and able to interfere with TF activity when delivered to target cells. Here, we review the inhibitory effects of decoy oligodeoxyribonucleotides (ODNs) on expression of IL-8 gene and secretion of IL-8 by cystic fibrosis cells infected by Pseudomonas aeruginosa. In addition, the effects of decoy molecules based on peptide nucleic acids (PNAs) are discussed. In this respect PNA-DNA-PNA (PDP) chimeras are interesting: (a) unlike PNAs, they can be complexed with liposomes and microspheres; (b) unlike oligodeoxyribonucleotides (ODNs), they are resistant to DNAses, serum and cytoplasmic extracts; (c) unlike PNA/PNA and PNA/DNA hybrids, they are potent decoy molecules. Interestingly, PDP/PDP NF-kappaB decoy chimeras inhibit accumulation of pro-inflammatory mRNAs (including IL-8 mRNA) in P. aeruginosa infected IB3-1, cells reproducing the effects of decoy oligonucleotides. The effects of PDP/PDP chimeras, unlike ODN-based decoys, are observed even in absence of protection with lipofectamine. Since IL-8 is pivotal in pro-inflammatory processes affecting cystic fibrosis, inhibition of its functions might have a clinical relevance.
10.1016/j.bcp.2010.06.047
Roles of IL-8 in ocular inflammations: a review.
Ghasemi Hassan,Ghazanfari Tooba,Yaraee Roya,Faghihzadeh Soghrat,Hassan Zuhair Mohammad
Ocular immunology and inflammation
INTRODUCTION:This review presents the current in vitro and in vivo animal and human research on the roles of IL-8 in ocular inflammatory diseases. MATERIALS AND METHODS:Data sources were a literature review using Pub Med, Medline, and ISI databases (from 1990 to 2011). Search items included interleukine-8 (IL-8), CXCL8, chemokines, cytokines, alone or in combination with the, serum, aqueous, vitreous, eye, ocular, ocular tissues, ophthalmic, and review. RESULTS:IL-8 may be involved in primary or secondary ocular inflammations. Ocular effects of IL-8 differ based on the source of the secretion and site of the action. The most important effects of IL-8 in the eyes are angiogenic activities and induction of ocular inflammation. CONCLUSION:IL-8 plays important roles in ocular inflammation and angiogenesis in conjunctiva, cornea, iris, retina, and orbit. Anti-IL-8 targeted immunotherapy has been introduced as an important treatment modality, provided that IL-8 signal blocking takes place in desired areas and tissues.
10.3109/09273948.2011.618902
Potential mechanism of interleukin-8 production from lung cancer cells: an involvement of EGF-EGFR-PI3K-Akt-Erk pathway.
Zhang Yong,Wang Linyan,Zhang Miaomiao,Jin Meiling,Bai Chunxue,Wang Xiangdong
Journal of cellular physiology
Tumor inflammatory microenvironment is considered to play the role in the sensitivity of tumor cells to therapies and prognosis of lung cancer patients. Interleukin-8 (IL-8) is one of critical chemo-attractants responsible for leukocyte recruitment, cancer proliferation, and angiogenesis. The present study aimed at investigating potential mechanism of IL-8 production from human non-small cell lung cancer (NSCLC) SPC-A1 cells. We initially found that EGF could directly stimulate IL-8 production, proliferation, and bio-behaviors of lung cancer cells through the activation of EGFR, PI3K, Akt, and Erk signal pathway. EGF-stimulated IL-8 production, phosphorylation of Akt and Erk, and cell proliferation and movement could be inhibited by EGFR inhibitor (Erlotinib), PI3K inhibitor (GDC-0941 BEZ-235 and SHBM1009), and ERK1/2 inhibitor (PD98059). Our data indicate that IL-8 production from lung cancer cells could be initiated by their own produced factors, leading to the recruitment of inflammatory cells in the cancer tissue, and the formation of inflammatory microenvironment. Thus, it seems that the signal pathway of EGFR-PI3K-Akt-Erk can be the potential target of therapies for inflammatory microenvironment in lung cancer.
10.1002/jcp.22722
Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its diagnostic and prognostic values. A review.
Kotyza Jaromír
The International journal of biological markers
Interleukin-8 (IL-8, CXCL8) was originally discovered as a powerful attractor and activator of polymorphonuclear leukocytes. It was soon recognized that IL-8 also affects proliferation and migration of cancer cells, tumor angiogenesis and metastasis, and that it is expressed in many cancerous cell types. IL-8 protein expression is usually increased in serum of cancer patients, but markedly higher concentrations are found in cancer-associated non-vascular extracellular fluids, such as pleural effusion, ascites and cyst fluid. Elevated concentrations of IL-8 are indicative of malignant processes also in cerebrospinal fluid, urine, saliva, interstitial fluid and cervicovaginal secretions. Higher IL-8 levels are typically found in high-grade peritumoral fluids rather than low-grade tumors and benign conditions, with the exception of inflammatory processes. In line with recent molecular biology investigations, it appears that the local IL-8 production is related to its malignant origin and to tumor progression. Hence, IL-8 in peritumoral fluid is to be taken into consideration while assessing tumor character and monitoring the tumor progression/remission status. Besides, the data here collected justify the attempts to find an IL-8-targeted inhibitory therapy
10.5301/JBM.2012.9261
Interleukin 8 and acute lung injury.
Allen Timothy Craig,Kurdowska Anna
Archives of pathology & laboratory medicine
Acute lung injury is a complex clinical syndrome involving acute inflammation, microvascular damage, and increased pulmonary vascular and epithelial permeability, frequently resulting in acute respiratory failure culminating in often-fatal acute respiratory distress syndrome. Interleukin 8 (IL-8), a potent neutrophil attractant and activator, plays a significant role in acute lung injury via the formation of anti-IL-8 autoantibody:IL-8 complexes and those complexes' interaction with FcγRIIa receptors, leading to the development of acute lung injury by, among other possible mechanisms, effecting neutrophil apoptosis. These complexes may also interact with lung endothelial cells in patients with acute respiratory distress syndrome. Continuing research of the role of neutrophils, IL-8, anti-IL-8 autoantibody:IL-8 complexes, and FcγRIIa receptors may ultimately provide molecular therapies that could lower acute respiratory distress syndrome mortality, as well as reduce or even prevent the development of acute lung injury altogether.
10.5858/arpa.2013-0182-RA
Quantitative assessment of the associations between interleukin-8 polymorphisms and periodontitis susceptibility.
Chen Xing,Huang Jinping,Zhong Liangjun,Ding Cheng
Journal of periodontology
BACKGROUND:This review assesses the associations of interleukin-8 gene (IL-8) -251A/T (rs4073) and -845T/C (rs2227532) polymorphisms with susceptibility to periodontitis. METHODS:Several electronic databases were searched for eligible articles. Twelve studies involving 2,233 cases and 2,655 controls were retrieved and analyzed. Odds ratios (ORs) along with 95% confidence intervals (CIs) were calculated to assess the strength of relationship between the IL-8 polymorphisms and periodontitis risk. RESULTS:No significant association was found for IL-8 -251A/T polymorphism with periodontitis in the overall analysis and stratification by periodontitis type and smoking status. Subgroup analysis by ethnicity revealed that -251A/T T allele and TT genotype were associated with decreased risk of periodontitis in a Brazilian mixed population (T allele versus A allele: OR 0.80, 95% CI 0.68 to 0.94, Pheterogeneity = 0.30; TT versus AA: OR 0.65, 95% CI 0.46 to 0.93, Pheterogeneity = 0.39; TT versus AA/AT:OR 0.58, 95% CI 0.35 to 0.98, Pheterogeneity = 0.01). In addition, -251A/T T allele was associated with increased periodontitis risk in Asians. Pooled estimates showed that the -845T/C polymorphism was associated with periodontitis susceptibility in overall analysis and the chronic periodontitis subgroup. In addition, marginal associations were observed between -845T/C polymorphism and periodontitis in a Brazilian mixed population. Moreover, this association was also confirmed to be significant in Brazilian non-smokers. CONCLUSION:This meta-analysis indicated that both IL-8 -251A/T and -845T/C polymorphisms may be involved in the development of periodontitis in a Brazilian mixed population, whereas the -251A/T allele T appeared to be a risk factor for periodontitis in Asians.
10.1902/jop.2014.140450
Interleukin-8: A critical chemokine in biliary atresia.
Dong Rui,Zheng Shan
Journal of gastroenterology and hepatology
Biliary atresia (BA) is characterized by periductular inflammation and fibrosis and is associated with the progressive obliteration of the bile ducts. The induction and maintenance of systemic and local inflammatory responses plays a pivotal role in this process. Interleukin-8 (IL-8) is an important mediator of inflammation and the immune response in human disease. IL-8 is overexpressed in BA, and its expression positively correlates with inflammation and liver fibrosis. In this review, we focus on the available evidence, recent insights, and future clinical and preclinical possibilities regarding the role of IL-8 in BA.
10.1111/jgh.12900
Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.
Jundi Karim,Greene Catherine M
Biomolecules
Interleukin-8 (IL-8) is a neutrophil chemokine that is encoded on the CXCL8 gene. Normally CXCL8 expression is repressed due to histone deacetylation, octamer-1 binding to the promoter and the inhibitory effect of nuclear factor-κB repressing factor (NRF). However, in response to a suitable stimulus, the human CXCL8 gene undergoes transcription due to its inducible promoter that is regulated by the transcription factors nuclear factor-κB (NF-κB), activating protein (AP-1), CAAT/enhancer-binding protein β (C/EBPβ, also known as NF-IL-6), C/EBP homologous protein (CHOP) and cAMP response element binding protein (CREB). CXCL8 mRNA is then stabilised by the activity of p38 mitogen-activated protein kinase (p38 MAPK). Cystic fibrosis (CF) lung disease is characterised by a neutrophil-dominated airway inflammatory response. A major factor contributing to the large number of neutrophils is the higher than normal levels of IL-8 that are present within the CF lung. Infection and inflammation, together with intrinsic alterations in CF airway cells are responsible for the abnormally high intrapulmonary levels of IL-8. Strategies to inhibit aberrantly high CXCL8 expression hold therapeutic potential for CF lung disease.
10.3390/biom5031386
Association between interleukin-8 levels and chronic periodontal disease: A PRISMA-compliant systematic review and meta-analysis.
Finoti Livia S,Nepomuceno Rafael,Pigossi Suzane C,Corbi Sâmia Ct,Secolin Rodrigo,Scarel-Caminaga Raquel M
Medicine
BACKGROUND:Current publications present contradictory findings regarding interleukin-8 (IL-8) levels in patients with chronic periodontitis (CP). This systematic review compile evidences of the IL8 mRNA and protein levels in gingival tissue, saliva, and gingival crevicular fluid (GCF) investigated in patients with CP. Moreover, 2 meta-analyses were made focusing on the IL-8 levels in GCF and saliva of patients with or without CP. METHODS:Electronic searches of the PubMed, Web of Science, and Scopus databases were conducted for publications up to February 2016 that investigated the levels of IL-8 detected in individuals with CP compared with health individuals. A total of 31 publications were included in the systematic review. For meta-analyses, the strength of association was calculated by pooled odds ratios with 95% confidence intervals using RevMan 5.1 software. Heterogeneity was examined using Higgins I-squared, tau-squared, and χ tests. RESULTS:In biopsies of gingival tissue of CP patients, all studies found higher IL8 mRNA levels, and the majority of studies showed higher IL-8 protein levels in this tissue of individuals with moderate to severe CP. Four studies investigating the IL-8 levels in saliva showed inconclusive results. In spite of some studies seemed to indicate higher levels of IL-8 in GCF of CP patients, the meta-analysis results showed significantly lower IL-8 levels (pg/μL) in GCF of CP patients in comparison with periodontally healthy subjects. CONCLUSIONS:We concluded that IL8 gene expression and IL-8 protein levels were higher in gingival tissues of CP patients when compared to periodontally health individuals. Meta-analysis of studies that measured IL-8 (pg/uL) in GCF found lower levels in CP patients. There are conflicting evidences regarding IL-8 levels in saliva.
10.1097/MD.0000000000006932
Abnormal peritoneal regulation of chemokine activation-The role of IL-8 in pathogenesis of endometriosis.
Sikora Justyna,Smycz-Kubańska Marta,Mielczarek-Palacz Aleksandra,Kondera-Anasz Zdzisława
American journal of reproductive immunology (New York, N.Y. : 1989)
PROBLEM:Endometriosis is a chronic inflammatory disease associated with an impairment in immune response. Disorders in the peritoneal fluid and ectopic endometrium macrophage populations and their secretory products create a specific microenvironment inducing the development of the disease. The important factors involved in inflammation associated with endometriosis are chemokines, especially interleukin (IL)-8. For this reason, the current study briefly reviews the role of IL-8 in the pathogenesis of endometriosis. METHOD OF STUDY:A systematic review was done on all published studies that compared IL-8 expression and concentration in patients with and without endometriosis to evaluate their potential as biomarkers for the disease. RESULTS:IL-8 induces chemotaxis of neutrophils and other immune cells; also, it is a potent angiogenic agent. Most researchers pointed to the increased peritoneal and serum IL-8 levels and showed correlation with the severity of the disease, size and number of the active lesions. IL-8 takes part in all processes during the development of the disease: adhesion, invasion, and implantation of ectopic tissue. Additionally, the chemokine plays a role in growth and maintenance of ectopic endometrial tissue directly affecting endometrial cell proliferation. IL-8 might also protect ectopic cells against death by apoptosis. CONCLUSION:It may act as an autocrine growth factor in the endometrium and promotes the vicious circle of endometrial cell attachment and, in consequence, may lead to a transformation from acute to chronic inflammation stage.
10.1111/aji.12622