title: Adiponectin confers protection from acute colitis and restricts a B cell immune response.
abstract: Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze thein vitroeffects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress.In vitro, adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1in vitro, these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Obeid
authors.affiliation: the Department of Molecular and Cell Biology and.
authors.forename: Miriam
authors.initials: M
authors.lastname: Wankell
authors.affiliation: the Department of Molecular and Cell Biology and.
authors.forename: Berenice
authors.initials: B
authors.lastname: Charrez
authors.affiliation: the Department of Molecular and Cell Biology and.
authors.forename: Jade
authors.initials: J
authors.lastname: Sternberg
authors.affiliation: the Department of Molecular and Cell Biology and.
authors.forename: Roxane
authors.initials: R
authors.lastname: Kreuter
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaili
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ramezani-Moghadam
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Devine
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Read
authors.affiliation: the University of Melbourne, Victoria, VIC 3010, Australia, and.
authors.forename: Prithi
authors.initials: P
authors.lastname: Bhathal
authors.affiliation: the Department of Molecular and Cell Biology and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lopata
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlensteil
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia, lionel.hebbard@jcu.edu.au.|the Department of Molecular and Cell Biology and.|Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: Lionel
authors.initials: L
authors.lastname: Hebbard
mesh_terms: D000208:Acute Disease; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003092:Colitis / Q000378:metabolism* / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D045325:HCT116 Cells; D006706:Homeostasis; D006801:Humans; D007107:Immune System; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054419:Receptors, Adiponectin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D016207:Cytokines; D054419:Receptors, Adiponectin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C475419:adiponectin receptor 1, mouse; D016264:Dextran Sulfate
keywords: STAT3; adiponectin; autoimmunity; colitis; obesity