Abstract

PCR 6 h later. Results: Intrarectal injection of TNBS produced severe colitis accompanied by body weight loss and diarrhea as well as increased MPO activity and ROS production in WT mice. The severity of colitis, body weight loss, diarrhea, increased MPO activity and ROS production were significantly reduced in NOX1KO mice. The expression of iNOS, TNF-[alpha], IL-1[beta], KC, MIP-2, and MCP-1 expressions was markedly upregulated after the injection of TNBS in WT mice, but all these responses were significantly lower in NOX1KO mice. On the other hand, the apparent expression NOX1 mRNA in addition to NOX2 mRNA was detected in both lamina propria and peritoneal macrophages isolated fromWTmice. The exposure of LPS to peritoneal macrophages isolated fromWTmice caused marked upregulation of iNOS, TNF-[alpha], and IL-1[beta] mRNAs, but these increases were significantly mitigated in peritoneal macrophages isolated from NOX1KO mice. Conclusion: These findings suggest that NOX1 plays an important role in the pathogenesis of TNBSinduced colitis by upregulating inflammatory mediators, including iNOS, cytokines, and chemokines. It is likely that the NOX1 expressed in colonic macrophages may play an important role in these responses. Therefore, NOX1 expressed in colonic macrophages may be a novel target for the treatment and prevention of inflammatory bowel diseases.

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