title: In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ogyi
authors.initials: O
authors.lastname: Park
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Honglei
authors.initials: H
authors.lastname: Weng
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Yin
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Ki
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Yoo
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000378:metabolism / Q000473:pathology; D003208:Concanavalin A / Q000009:adverse effects; D004052:Diethylnitrosamine / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006498:Hepatectomy; D006509:Hepatitis B / Q000378:metabolism / Q000473:pathology; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000097043:Interleukin-22
chemical_list: D003208:Concanavalin A; D004052:Diethylnitrosamine; D007378:Interleukins; D000097043:Interleukin-22