Intestinal epithelial suppressor of cytokine signaling 3 enhances microbial-induced inflammatory tumor necrosis factor-α, contributing to epithelial barrier dysfunction.
Bottom Line: Activation of TLR5 signaling pathways, compared with other TLR, increases TNF-α mRNA in a dose-dependent manner and SOCS3 enhances TLR5-induced TNF-α.We also show that flagellin promotes transcription of TNFR2 and that SOCS3 limits this expression, presenting a mechanism of SOCS3 action.Our data also support the role of microbial ligands in epithelial wound healing and suggest that a functional consequence of increased TNF-α is reduced wound healing.
Affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK; and.Show MeSH
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Mentions: We performed immunocytochemistry and Western blots to assess how TLR5 stimulation impacted on IEC TNFR2 protein expression. TNFR2 expression appeared reduced within 1 h at the cell surface receptor level and was regained to baseline by 6 h after flagellin treatment (Fig. 4A). SOCS3 overexpression may delay TNFR2 return to baseline levels, but expression appeared equivalent to that of control cells 12 h following treatment. Flagellin did not appear to impact of TNFR1 expression (Fig. 4B).
Affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK; and.