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Toll‐like receptor 5 (TLR5), but not TLR4 or 3, induces TNFα production by intestinal epithelial cells (IEC), which is enhanced by suppressor of cytokine signalling 3 (SOCS3)
Author(s) -
Thagia Imtiyaz,
Rigby Rachael
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1108.5
Subject(s) - socs3 , tlr5 , tlr4 , downregulation and upregulation , cytokine , stimulation , receptor , microbiology and biotechnology , chemistry , inflammation , biology , cancer research , immunology , signal transduction , endocrinology , tlr2 , stat3 , biochemistry , gene
A single layer of IEC, expressing TLR, line the intestine. TLR‐induced inflammatory pathways are vital for mucosal homeostasis and dysregulated repair may predispose to inflammatory bowel disease (IBD). In IBD, the expression of SOCS3, a negative feedback inhibitor of the JAK/STAT pathway, is enhanced. The aim of this study was to establish the function of SOCS3 in TLR‐mediated epithelial homeostasis. We developed SW480 IEC cell lines to over‐express SOCS3 (SOCS3 hi ), to study gene expression, vs. SOCS3 norm IEC in response to microbial stimulation. IEC production of pro‐inflammatory TNFα mRNA was upregulated following stimulation with flagellin (TLR5), but not LPS (TLR4) or Poly I:C (TLR3), at varying concentrations. This response was significantly enhanced in SOCS3 hi vs. SOCS3 norm IEC: 31.9 ± 10 vs. 8.7 ± 1.8 fold increase at 1ug/ml (p≤0.05), 20.3 ± 4.4 vs. 6.4 ± 1.6 fold‐increase at 0.1ug/ml (p≤0.03) and 15.1 ± 5.1 vs. 4 ± 1.1 fold‐increase at 0.01ug/ml (p≤0.05), compared with no‐treatment control mRNA levels. Our studies indicate that SOCS3 is not only an inhibitor of epithelial repair, but may help to perpetuate the inflammatory response by promoting the production of pro‐inflammatory TNFα.