title: Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway.
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-X(L), 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.
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
authors.forename: Dechun
authors.initials: D
authors.lastname: Feng
authors.forename: Ogyi
authors.initials: O
authors.lastname: Park
authors.forename: Svetlana
authors.initials: S
authors.lastname: Radaeva
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Shi
authors.initials: S
authors.lastname: Yin
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Kong
authors.forename: Mingquan
authors.initials: M
authors.lastname: Zheng
authors.forename: Sam
authors.initials: S
authors.lastname: Zakhari
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002108:Ceruletide; D007378:Interleukins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D002108:Ceruletide; D007378:Interleukins; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D000097043:Interleukin-22; C494812:Bcl2l1 protein, mouse