Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway

Dechun Feng, Ogyi Park, Svetlana Radaeva, Hua Wang, Shi Yin, Xiaoni Kong, Mingquan Zheng, Sam Zakhari, Jay K. Kolls, Bin Gao

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-XL, which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalInternational Journal of Biological Sciences
Volume8
Issue number2
DOIs
StatePublished - Jan 6 2012

Keywords

  • Autophagy
  • Bcl-2
  • Beclin-1
  • IL-22
  • Pancreatitis

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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