Adiponectin confers protection from acute colitis and restricts a B cell immune response

Obeid, Stephanie, Wankell, Miriam, Charrez, Berenice, Sternberg, Jade, Kreuter, Roxane, Esmaili, Saeed, Ramezani-Moghadam, Mehdi, Devine, Carol, Read, Scott, Bhathal, Prithi, Lopata, Andreas, Ahlenstiel, Golo, Qiao, Liang, George, Jacob, and Hebbard, Lionel (2017) Adiponectin confers protection from acute colitis and restricts a B cell immune response. Journal of Biological Chemistry, 292 (16). pp. 6569-6582.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: http://dx.doi.org/10.1074/jbc.M115.71264...
 
9
6


Abstract

Adiponectin demonstrates beneficial effects in various metabolic diseases including diabetes, and in bowel cancer. Recent data also suggests 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-knockout mice were orally administered dextran sulfate sodium for 7 days, and were compared to wild-type mice. The severity of disease was analysed histopathologically, and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyse the in vitro effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin-knockout mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration and an increased presence of activated B cells compared to controls. This was accompanied by an exaggerated pro-inflammatory cytokine profile and increased STAT3 signalling. Adiponectin-knockout 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 signalling. Following the abrogation of AdipoR1 in vitro, these protective effects of adiponectin were abolished. In sum, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.

Item ID: 47667
Item Type: Article (Research - C1)
ISSN: 1083-351X
Keywords: adiponectin, colitis, STAT3, autoimmunity, obesity
Funders: Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney, National Health and Medical Research Council of Australia (NHMRC), Cancer Council NSW (CC), Cancer Council Queensland (CCQ), James Cook University (JCU)
Projects and Grants: NHMRC #APP1053206, 1047417 & 1087297, CC NSW #1070076 & 1069733, CCQ #1123436, JCU Development Grant 2016
Date Deposited: 13 Mar 2017 22:34
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
Downloads: Total: 6
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page