JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (6): 1-6.doi: 10.6040/j.issn.1671-7554.0.2015.001

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IL-22 protects mice from acute severe pancreatitis via STAT3 signaling pathway

BAI Jinxia1, BAI Jinyun2, SHI Xiuju1, XU Hongwei1   

  1. 1. Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. School of Medicine, Shandong University, Jinan 250012, Shandong, China
  • Received:2015-01-04 Revised:2015-03-31 Online:2015-06-10 Published:2015-06-10

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Abstract: Objective To investigate the effect of interleukin-22 (IL-22) in acute severe pancreatitis (SAP) induced by L-arginine and its signal pathway. Methods Sixty male Balb/c mice were randomly divided into 4 groups, the normal control group(NaCl group, n=10), SAP group(n=30), treatment control group (PBS group, n=10) and treatment group(rIL-22 group, n=10). Mice were induced intraperitoneally with L-arginine(two doses, 4 g/kg each, 1 hour apart). PBS or rIL-22 (200 ng/time, 5 times) was administrated to mice at the indicated times in PBS and rIL-22 groups. Serum amylase and pancreas tissue histopathology were examined. IL-22RA1, regenerating islet-dedrived protein 3β(Reg3β), Reg3γ, B cell lymphoma/lewmia-2(Bcl-2), Bcl-xL mRNA were detected by Real-time PCR. STAT3 expression and activation were assessed by Western blotting. Mortality ratios in PBS and IL-22 group were counted. Results Seventy-two hours after L-arginine administration, typically histopathological changes were observed in SAP group. The expressions of Reg3β, Reg3γ, Bcl-2 and Bcl-xL mRNA decreased progressively, while serum amylaseand IL-22RA1 mRNA increased until 48 hours, but decreased apparently at 72 hours. Compared with those in PBS group, rIL-22 group showed lower serum amylase(P<0.05), slighter pathological changes and lower mortality(P<0.05). Compared with those in PBS group, the expressions of Reg3β, Reg3γ, Bcl-2, Bcl-xL, IL-22RA1 mRNA and phospho-STAT3 protein in rIL-22 group markedly increased(P<0.05). Conclusion Exogenous recombinant IL-22 protects mice from L-arginine induced SAP by enhancing the expressions of antimicrobial peptides and antiapoptotic genes through the STAT3 signaling pathway.

Key words: Signal transducer and activator transcription 3, Interleukin-22, Acute severe pancreatitis, Antimicrobial peptide

CLC Number: 

  • R576
[1] Rendon JL, Li X, Akhtar S, et al. Interleukin-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury[J]. Shock, 2013, 39(1):11-18.
[2] Chestovich PJ, Uchida Y, Chang W, et al. Interleukin-22: implications for liver ischemia-reperfusion injury[J]. Transplantation, 2012, 93(5):485-492.
[3] Choi SM, McAleer JP, Zheng M, et al. Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia[J]. J Exp Med, 2013, 210(3):551-561.
[4] 杨学超,杨松巍,杨光,等.白细胞介素-22对缺氧条件下肠上皮屏障的保护作用及其机制[J].中华实验外科杂志,2013,30(3):476-479. YANG Xuechao, YANG Songwei, YANG Guang, et al. Preventive effect of interleukin-22 on epithelial barrier function of T84 cells under hypoxia and possible mechanism[J]. Chin J Exp Surg, 2013, 30(3):476-479.
[5] Dawra R, Sharif R, Phillips P, et al. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 292(4):G1009-1018.
[6] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods, 2001, 25(4):402-408.
[7] Dumoutier L, Lejeune D, Colau D, et al. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22[J]. J Immunol, 2001, 166(12):7090-7095.
[8] Ouyang W, Rutz S, Crellin NK, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease[J]. Annu Rev Immunol, 2011, 29:71-109. doi: 10.1146/annurev-immunol-031210-101312.
[9] Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22[J]. Nat Immunol, 2011, 12(5):383-390.
[10] Zenewicz LA, Flavell RA. Recent advances in IL-22 biology[J]. Int Immunol, 2011, 23(3):159-163.
[11] Wolk K, Kunz S, Witte E, et al. IL-22 increases the innate immunity of tissues[J]. Immunity, 2004, 21(2):241-254.
[12] Gurney AL. IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues[J]. Int Immunopharmacol, 2004, 4(5):669-677.
[13] Xie MH, Aggarwal S, Ho WH, et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R[J]. J Biol Chem, 2000, 275(40):31335-31339.
[14] Pickert G, Neufert C, Leppkes M, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing[J]. J Exp Med, 2009, 206(7):1465-1472.
[15] Parikh A, Stephan AF, Tzanakakis ES. Regenerating proteins and their expression, regulation and signaling[J]. Biomol Concepts, 2012, 3(1):57-70.
[16] Gironella M, Folch-Puy E, LeGoffic A, et al. Experimental acute pancreatitis in PAP/HIP knock-out mice[J]. Gut, 2007, 56(8):1091-1097.
[17] Lin YY, Viterbo D, Mueller CM, et al. Small-interference RNA gene knockdown of pancreatitis-associated proteins in rat acute pancreatitis[J]. Pancreas, 2008, 36(4):402-410.
[18] Czabotar PE, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy[J]. Nat Rev Mol Cell Biol, 2014, 15(1):49-63.
[19] Sung KF, Odinokova IV, Mareninova OA, et al. Prosurvival Bcl-2 proteins stabilize pancreatic mitochondria and protect against necrosis in experimental pancreatitis[J]. Exp Cell Res, 2009, 315(11):1975-1989.
[20] Xue J, Nguyen DT, Habtezion A. Aryl hydrocarbon receptor regulates pancreatic IL-22 production and protects mice from acute pancreatitis[J]. Gastroenterology, 2012, 143(6):1670-1680.
[21] Zheng Y, Valdez PA, Danilenko DM, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens[J]. Nat Med, 2008, 14(3):282-289.
[22] Radaeva S, Sun R, Pan HN, et al. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation[J]. Hepatology, 2004, 39(5):1332-1342.
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