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In vivo consequences of liver‐specific interleukin‐22 expression in mice: Implications for human liver disease progression
Author(s) -
Park Ogyi,
Wang Hua,
Weng Honglei,
Feigenbaum Lionel,
Li Hai,
Yin Shi,
Ki Sung Hwan,
Yoo Seong Ho,
Dooley Steven,
Wang FuSheng,
Young Howard A.,
Gao Bin
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24339
Subject(s) - inflammation , proinflammatory cytokine , liver disease , hepatocyte , cytokine , liver regeneration , biology , interleukin , hepatitis , liver cancer , immunology , genetically modified mouse , medicine , transgene , hepatocellular carcinoma , cancer research , regeneration (biology) , in vitro , gene , microbiology and biotechnology , biochemistry
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. (H EPATOLOGY 2011;)