Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5023-5032
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5023
Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Author contributions: Qiao YY, Liu XQ and Xu HW designed the experiments; Qiao YY, Liu XQ, Xu CQ, Zhang Z and Xu HW performed the research; Xu CQ and Xu HW contributed new reagents/analytic tools; Qiao YY, Zhang Z and Xu HW analyzed the data; Qiao YY and Liu XQ wrote the paper; Xu CQ and Xu HW revised the manuscript.
Supported by the Shandong Provincial Science and Technology Committee of China, No. 2014GGH218034.
Institutional review board statement: The study was reviewed and approved by Institutional Review Board of the Shandong Provincial Hospital Affiliated to Shandong University.
Institutional animal care and use committee statement: All animal experiments were carried out with approval by an ethics committee in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and further approved by the Institutional Care Committee (Shandong University, Jinan, China).
Conflict-of-interest statement: None of the authors have any possible conflicts of interest.
Data sharing statement: There are no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Weiqi Road, Huai Yin District, Jinan 250021, Shandong Province, China. xu_hong_wei@sina.com
Telephone: +86-531-68776350 Fax: +86-531-87068344
Received: February 15, 2016
Peer-review started: February 17, 2016
First decision: March 21, 2016
Revised: April 11, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 7, 2016
Abstract

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved.

METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot.

RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05).

CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.

Keywords: Interleukin-22, Acute severe pancreatitis, Lung injury, Anti-apoptosis gene, Signal transducer and activator of transcription 3

Core tip: Interleukin-22 (IL-22) is recognized today as a key player in the antimicrobial defense, regeneration, and protection against damage. However, no reports have described the effects of IL-22 on acute severe pancreatitis (SAP)-associated lung injury. In this study, we found that IL-22 alleviated SAP-associated lung injury in mice by enhancing the expression of anti-apoptosis genes, such as Bcl-2 and Bcl-xL, through the STAT3 signaling pathway. Therefore, IL-22 and the components of STAT3 signaling pathway may be promising targets in the treatment of SAP-associated lung injury.