In vivo consequences of liver-specific interleukin-22 expression in mice: implications for human liver disease progression
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 acti...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 April 2011
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| In: |
Hepatology
Year: 2011, Volume: 54, Issue: 1, Pages: 252-261 |
| ISSN: | 1527-3350 |
| DOI: | 10.1002/hep.24339 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/hep.24339
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| Author Notes: | Ogyi Park, Hua Wang, Honglei Weng, Lionel Feigenbaum, Hai Li, Shi Yin, Sung Hwan Ki, Seong Ho Yoo, Steven Dooley, Fu-Sheng Wang, Howard A. Young, and Bin Gao |
| Summary: | 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. |
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| Item Description: | Gesehen am 09.09.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1527-3350 |
| DOI: | 10.1002/hep.24339 |