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VSL#3 Probiotic Stimulates T‐Cell Protein Tyrosine Phosphatase‐Mediated Protection of Intestinal Epithelial Barrier Function
Author(s) -
Krishnan Moorthy,
Shah Nilay,
Penrose Harrison,
Marchelletta Ronald,
McCole Declan
Publication year - 2015
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.29.1_supplement.857.1
Subject(s) - protein tyrosine phosphatase , barrier function , inflammatory bowel disease , phosphatase , cytokine , probiotic , intestinal epithelium , signal transduction , phosphorylation , immunology , cancer research , epithelium , medicine , microbiology and biotechnology , biology , disease , pathology , genetics , bacteria
VSL#3 is a probiotic cocktail that has shown efficacy in treating murine colitis and patients with ulcerative colitis. VSL#3 can also exert a beneficial effect on epithelial barrier function which is dysregulated in inflammatory bowel disease (IBD). We have previously shown that the enzyme T‐cell protein tyrosine phosphatase (TCPTP), encoded by the IBD candidate gene PTPN2 , protects intestinal epithelial barrier function. The aim of this study was to identify if VSL#3 activates TCPTP and protects intestinal epithelial cells (IEC) from the effects of the IBD‐associated pro‐inflammatory cytokine interferon‐gamma (IFN‐γ). Administration of VSL#3 to T84 or HT‐29 IEC polarized monolayers increased expression and enzymatic activity of TCPTP in a dose‐dependent and time‐dependent manner. VSL#3 reduced IFN‐γ signaling, as reflected by decreased phosphorylation of STAT‐1, in a TCPTP‐dependent manner. In addition, VSL#3 alone increased IEC barrier integrity and promoted recovery of barrier function in IFN‐γ pre‐treated IEC monolayers. VSL#3 conditioned medium also promoted partial recovery from IFN‐γ‐induced barrier defects. Using a stable TCPTP‐deficient HT‐29 cell line, we observed that the recovery of TER induced by VSL#3 in IFN‐γ treated cells was TCPTP‐dependent. In conclusion, the probiotic VSL#3 increased activity and expression of TCPTP to reduce inflammatory signaling and correct epithelial barrier defects.