Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2013; 19(17): 2638-2649
Published online May 7, 2013. doi: 10.3748/wjg.v19.i17.2638
Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis
Lian-Zhen Yu, Hai-Yang Wang, Shu-Ping Yang, Zhi-Ping Yuan, Fang-Yuan Xu, Chao Sun, Rui-Hua Shi
Lian-Zhen Yu, Shu-Ping Yang, Zhi-Ping Yuan, Fang-Yuan Xu, Chao Sun, Rui-Hua Shi, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Hai-Yang Wang, Department of Internal Medicine, Affiliated Mingde Hospital of Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
Author contributions: Yu LZ and Wang HY contributed equally to this work; Wang HY, Yu LZ and Shi RH designed the research; Wang HY, Yu LZ, Yang SP, Yuan ZP, Xu FY and Sun C performed the research; Wang HY, Yu LZ, Yuan ZP, Xu FY and Sun C analyzed the data; Wang HY and Yu LZ wrote the paper.
Supported by National Natural Science Foundation of China, No. 81072692 and Natural Science Foundation of Jiangsu Higher Education Institutions of China, No. 10KJB320007
Correspondence to: Rui-Hua Shi, MD, PhD, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. ruihuashi@126.com
Telephone: +86-25-83674636 Fax: +86-25-83674636
Received: August 14, 2012
Revised: January 31, 2013
Accepted: February 8, 2013
Published online: May 7, 2013
Processing time: 257 Days and 1 Hours
Abstract

AIM: To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis.

METHODS: Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p-STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting.

RESULTS: Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.

CONCLUSION: IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.

Keywords: Ulcerative colitis; Ulcerative colitis-related carcinogenesis; Interleukin-22; Interleukin-22R1; STAT3

Core tip: This study investigates the expression of interleukin (IL)-22, IL-22R1, IL-23, and STAT3 in ulcerative colitis (UC) and UC-related carcinogenesis (UC-CRC) tissues from human and mouse. The results showed that IL-22 and related proteins were closely related to the severity of colitis, and the expression level of IL-22 and related proteins was higher in dysplasia tissues. IL-22/STAT3 signaling pathway was related to UC and UC-CRC. IL-22 can be used as a biomarker for determining the severity of UC and as an interesting therapeutic target in active UC and UC-CRC.