The absence of Nrf2 enhances NF-κB-dependent inflammation following scratch injury in mouse primary cultured astrocytes. Pan Hao,Wang Handong,Wang Xiaoliang,Zhu Lin,Mao Lei Mediators of inflammation It has been proved that Nrf2 depletion enhances inflammatory process through activation of NF-κB in the brain after TBI, but little is known about the relationship between Nrf2 and NF-κB in astrocytes after TBI. Hence, we used primary cultured astrocytes from either Nrf2 wildtype or knockout mice to study the influence of Nrf2 on the activation of NF-κB and expression of proinflammatory cytokines in a model of TBI in vitro. Primary cultured astrocytes were scratched to mimic the traumatic injury in vitro. Then the DNA-binding activity of NF-κB was evaluated by EMSA. The mRNA and protein levels of TNF-α, IL-1β, IL-6, and MMP9 were also evaluated. Gelatin zymography was performed to detect the activity of MMP9. The activity of NF-κB and expression of proinflammatory cytokines mentioned above were upregulated at 24 h after scratch. The expression and activity of MMP9 were also elevated. And such tendency was much more prominent in Nrf2 KO astrocytes than that in WT astrocytes. These results suggest that the absence of Nrf2 may induce more aggressive inflammation through activation of NF-κB and downstream proinflammatory cytokines in astrocytes. 10.1155/2012/217580

Nrf2 signaling pathway: Pivotal roles in inflammation. Ahmed Syed Minhaj Uddin,Luo Lin,Namani Akhileshwar,Wang Xiu Jun,Tang Xiuwen Biochimica et biophysica acta. Molecular basis of disease Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation. Therefore, the identification of new Nrf2-dependent anti-inflammatory phytochemicals has become a key point in drug discovery. In this review, we discuss the members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway. In addition we also discuss about the regulation of NLRP3 inflammasome by Nrf2. Besides this, we summarize the current scenario of the development of anti-inflammatory phytochemicals and others that mediate the Nrf2/ARE signaling pathway. 10.1016/j.bbadis.2016.11.005

Depletion of Nrf2 enhances inflammation induced by oxyhemoglobin in cultured mice astrocytes. Pan Hao,Wang Handong,Zhu Lin,Mao Lei,Qiao Liang,Su Xingfen Neurochemical research Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element pathway has been proved to be the key regulator in reducing inflammatory damage, which is involved in subarachnoid hemorrhage (SAH). Here, in a traditional in vitro SAH model, we investigated the effect of Nrf2 depletion on pro-inflammatory cytokines production. Primary cultured astrocytes from Nrf2 wild type (WT) or knockout (KO) mouse were exposed or not exposed to oxyhemoglobin (OxyHb). Then the DNA-binding activity of transcription factor nuclear factor-κB (NF-κB) was detected by EMSA. The expression of TNF-α, IL-1β, IL-6 and MMP9 were evaluated. The activity of MMP9 was measured by Gelatin zymography. After exposure to OxyHb, NF-κB was activated and the expression of downstream pro-inflammatory cytokines was up-regulated in astrocytes. And such up-regulation was much higher in KO astrocytes than in WT astrocytes, which means more aggravated inflammation in Nrf2 deficient astrocytes. These results suggest that astrocytes participate in inflammatory process after SAH and the absence of Nrf2 may induce more aggressive inflammation through activation of NF-κB pathway. 10.1007/s11064-011-0571-6