title: Interferon-γ suppresses intestinal epithelial aquaporin-1 expression via Janus kinase and STAT3 activation.
abstract: Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway.
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Michael S
authors: MS
authors: Dicay
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Christina L
authors: CL
authors: Hirota
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Natalie J
authors: NJ
authors: Ronaghan
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Michael A
authors: MA
authors: Peplowski
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Raza S
authors: RS
authors: Zaheer
authors: Department of Anatomy and Histology, Flinders University, Bedford Park, Australia.
authors: Colin A
authors: CA
authors: Carati
authors: Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors: Wallace K
authors: WK
authors: MacNaughton
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050836:Interferon Regulatory Factor-2 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology*; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013997:Time Factors
chemical_list: D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D051398:Aquaporin 1; D007371:Interferon-gamma; D053612:Janus Kinases