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Hepatoprotective and anti‐fibrotic functions of interleukin‐22: Therapeutic potential for the treatment of alcoholic liver disease
Author(s) -
Kong Xiaoni,
Feng Dechun,
Mathews Stephanie,
Gao Bin
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12032
Subject(s) - stat protein , hepatic stellate cell , progenitor cell , liver injury , medicine , cancer research , cytokine , in vivo , stat3 , liver regeneration , alcoholic liver disease , interleukin , fibrosis , signal transduction , immunology , stem cell , microbiology and biotechnology , biology , pharmacology , pathology , regeneration (biology) , cirrhosis
Interleukin‐22 ( IL ‐22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL ‐22 R 1, which is generally thought to be expressed exclusively in epithelial cells, and IL ‐10 R 2. Our laboratory previously demonstrated that IL ‐22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL ‐22 R 1 and IL ‐10 R 2. Recently, we have identified high expression levels of IL ‐22 R 1 and IL ‐10 R 2 in liver progenitor cells and hepatic stellate cells ( HSCs ). Overexpression of IL ‐22 in vivo or treatment with IL ‐22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 ( STAT 3)‐dependent mechanism. IL ‐22 treatment also prevents HSC apoptosis in vitro and in vivo . Surprisingly, overexpression of IL ‐22, via either gene targeting or exogenous administration of adenovirus expressing IL ‐22, reduces liver fibrosis and accelerates the resolution of liver fibrosis during recovery. The anti‐fibrotic effects of IL ‐22 are mediated via the activation of STAT 3 in HSCs and subsequent induction of suppressor of cytokine signaling 3, which induces HSC senescence. Taken together, the hepatoprotective, mitogenic, and anti‐fibrotic effects of IL ‐22 are beneficial in ameliorating alcoholic liver injury. Importantly, due to the restricted expression of IL ‐22 R 1, IL ‐22 therapy is expected to have few side effects, thus making IL ‐22 a potential candidate for treatment of alcoholic liver disease.