Int J Biol Sci 2012; 8(2):249-257. doi:10.7150/ijbs.3967

Research Paper

Interleukin-22 Ameliorates Cerulein-Induced Pancreatitis in Mice by Inhibiting the Autophagic Pathway

Dechun Feng1#, Ogyi Park1#, Svetlana Radaeva2, Hua Wang1, Shi Yin1, Xiaoni Kong1, Mingquan Zheng3, Sam Zakhari2, Jay K. Kolls3, Bin Gao1 ✉

1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA;
2. Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA;
3. Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
# DF and OP contributed equally to this work.

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.

Keywords: IL-22, pancreatitis, autophagy, Bcl-2, Beclin-1.

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How to cite this article:
Feng D, Park O, Radaeva S, Wang H, Yin S, Kong X, Zheng M, Zakhari S, Kolls JK, Gao B. Interleukin-22 Ameliorates Cerulein-Induced Pancreatitis in Mice by Inhibiting the Autophagic Pathway. Int J Biol Sci 2012; 8(2):249-257. doi:10.7150/ijbs.3967. Available from http://www.ijbs.com/v08p0249.htm