Effect of adiponectin on murine colitis induced by dextran sulfate sodium.
OBJECTIVE
Adiponectin, an adipose tissue-derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of adiponectin on intestinal inflammation.


METHODS
We investigated the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin expression system. We also examined the contribution of adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of adiponectin on intestinal epithelial cells.


RESULTS
After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells.


CONCLUSIONS
Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.
Nishihara
Tamao
T
Department of Medicine and Pathophysiology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. tamaon@mr-path.med.osaka-u.ac.jp
Matsuda
Morihiro
M
Araki
Hiroshi
H
Oshima
Kazuya
K
Kihara
Shinji
S
Funahashi
Tohru
T
Shimomura
Iichiro
I
D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D016207:Cytokines; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D016264:Dextran Sulfate