Development of new treatment for the patients with inflammatory bowel disease by adiponectin
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Osaka University|
KIYOHARA Tatsuya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50322178)
FUNAHASI Toru Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (60243234)
TSUTSUI Shusaku Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10359846)
|Project Period (FY)
2003 – 2004
Completed(Fiscal Year 2004)
|Budget Amount *help
¥11,500,000 (Direct Cost : ¥11,500,000)
Fiscal Year 2004 : ¥5,500,000 (Direct Cost : ¥5,500,000)
Fiscal Year 2003 : ¥6,000,000 (Direct Cost : ¥6,000,000)
|Keywords||Adiponectin / Adiponectin deficient mice / IL-10 deficient mice / Crohn's disease / DSS colitis / アディポネクチン過剰発現 / アディポネタチン欠損マウス|
1)Profile of adiponectin expression in the hypertrophied mesenteric adipose tissue of the patients with inflammatory bowel disease.
Gene expression and production of adiponectin were examined in the hypertrophied mesenteric adipose tissue, fat wrapping of the patients with Crohn's disease(CD) by using semi-quantitative PCR and ELISA, respectively. mRNA expression and protein consentration of adiponectin were significantly increased in fat wrapping as compared with control tissues. CD patients with internal fistula demonstrated a significant decrease in gene expression and concentration of adiponectin in fat wrapping compared with those without internal fistula.
2)Effect of adiponectin on cytokine production by macrophages.
To evaluate anti-inflammatory effects of adiponectin, regulation of cytokine production from LPS-stimulated macrophages by adiponectin was examined in vitro. Adiponectin significantly inhibited TNFα and IL-12 production by LPS-stimulated peritoneal macrophages obtained
from IL-10 deficient mice.
3)The severity of colitis of adiponectin/IL-10 double knockout mice.
The role of adiponectin on intestinal inflammation of IL-10 deficient mice was tested by using adiponectin/IL-10 double knockout mice. Adiponectin deficiency showed no influence on the severity of colitis, survival and carcinogenesis of IL-10 knockout mice. This result may be explained by the possible involvement of IL-10 in anti-inflammatory effects of adiponectin.
4)Susceptibility of adiponectin deficient mice to experimental colitis.
To further elucidate an anti-inflammatory role of adiponectin in intestinal inflammation, the severity of dextran sulfate sodium(DSS)-induced colitis was examined in adiponectin deficient mice. Clinical disease activity, survival and histological features showed no difference between adiponectin deficient and wild-type mice. However, adiponectin deficient mice were induced colitis by low dose DSS treatment that did not influence wild-type mice.
5)Prevention of DSS-induced colitis by the treatment with adiponectin.
Preventive role of adiponectin intestinal inflammation was examined by using an adenovirus-mediated adiponectin-expression system. Injection of adenovirus producing adiponectin has significantly reduced the disease activities of adiponectin deficient mice with DSS-induced colitis. Less
Research Products (20results)