한빛사 논문
Abstract
Ogyi Park1,‡, Hua Wang1,‡, Honglei Weng3,‡, Lionel Feigenbaum4, Hai Li6, Shi Yin1, Sung Hwan Ki1, Seong Ho Yoo2, Steven Dooley3, Fu-Sheng Wang7, Howard A. Young5, Bin Gao1,*,§
1Laboratory of Liver Diseases and the
2Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD; the
3Molecular Hepatology-Alcohol Associated Diseases, II, Medical Clinic, Medical Faculty Mannheim at Heidelberg University, Mannheim, Germany; the
4Laboratory of Animal Science Program, Center for Cancer Research and the
5Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD; the
6Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China; and the
7Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China
Email: Bin Gao
*Correspondence: Bin Gao, M.D., Ph.D., Laboratory of Liver Diseases, NIAAA/NIH, 5625 Fishers Lane, Bethesda, MD 20892
Abstract
Interleukin-22 (IL-22), which acts as either a proinflammatory or anti-inflammatory cytokine in various disease models, is markedly up-regulated in chronic liver diseases, including hepatitis B and C. In this report, we demonstrate a strong correlation between IL-22 expression in the liver with active, inflammatory human liver disease. To clarify the role of IL-22 up-regulation in the pathogenesis of liver diseases, liver-specific IL-22 transgenic (IL-22TG) mice, under the control of albumin promoter, were developed. Despite elevated IL-22 serum levels ranging from 4,000 to 7,000 pg/mL, IL-22TG mice developed normally without obvious adverse phenotypes or evidence of chronic inflammation (except for slightly thicker epidermis and minor inflammation of the skin) compared with wild-type mice. Interestingly, IL-22TG mice were completely resistant to concanavalin A-induced T cell hepatitis with minimal effect on liver inflammation and had accelerated liver regeneration after partial hepatectomy. Although they did not spontaneously develop liver tumors, IL-22TG mice were more susceptible to diethylnitrosamine-induced liver cancer. Microarray analyses revealed that a variety of antioxidant, mitogenic, acute phase genes were up-regulated in the livers of IL-22TG mice compared with those from wild-type mice. Conclusion: These findings indicate that localized production of IL-22 in the liver promotes hepatocyte survival and proliferation but primes the liver to be more susceptible to tumor development without significantly affecting liver inflammation. (HEPATOLOGY 2011;)
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