INOS signaling interacts with COX-2 pathway in colonic fibroblasts

Yingting Zhu, Min Zhu, Peter Lance

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

COX-2 and iNOS are two major inflammatory mediators implicated in colorectal inflammation and cancer. Previously, the role of colorectal fibroblasts involved in regulation of COX-2 and iNOS expression was largely ignored. In addition, the combined interaction of COX-2 and iNOS signalings and their significance in the progression of colorectal inflammation and cancer within the fibroblasts have received little investigation. To address those issues, we investigated the role of colonic fibroblasts in the regulation of COX-2 and iNOS gene expression, and explored possible mechanisms of interaction between COX-2 and iNOS signalings using a colonic CCD-18Co fibroblast line and LPS, a potential stimulator of COX-2 and iNOS. Our results clearly demonstrated that LPS activated COX-2 gene expression and enhanced PGE2 production, stimulated iNOS gene expression and promoted NO production in the fibroblasts. Interestingly, activation of COX-2 signaling by LPS was not involved in activation of iNOS signaling, while activation of iNOS signaling by LPS contributed in part to activation of COX-2 signaling. Further analysis indicated that PKC plays a major role in the activation and interaction of COX-2 and iNOS signalings induced by LPS in the fibroblasts.

Original languageEnglish (US)
Pages (from-to)2116-2127
Number of pages12
JournalExperimental Cell Research
Volume318
Issue number16
DOIs
StatePublished - Oct 1 2012

Keywords

  • Cyclooxygenase-2
  • Inducible nitric oxide synthase
  • Lypopolysaccharide
  • Nitric oxide
  • Protein kianse C

ASJC Scopus subject areas

  • Cell Biology

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