%0 Journal Article
%T High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease
%A Lu Song
%A Rui Zhou
%A Sha Huang
%A Feng Zhou
%A Shufang Xu
%A Wei Wang
%A Fengming Yi
%A Xiaobing Wang
%A Bing Xia
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/425915
%X Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohn¡¯s disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population. 1. Introduction Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract which includes ulcerative colitis (UC) and Crohn¡¯s disease (CD). IBD is caused by complex interactions of genetic, immunoregulatory factors, intestinal microbiota, and environmental factors. Of these, genetic susceptibility of IBD has been demonstrated as a key factor by traditionally epidemiological studies [1]. Genome-wide association (GWA) studies have discovered some IBD susceptibility genes in interleukin-23/T-helper 17 (IL-23/Th17) pathway, such as IL-12B, IL-23R, Janus kinase 2 gene (JAK2), signal transducer and activator of transcription 3 (STAT3) and tumor necrosis factor (ligand) superfamily member 15 (TNFSF15) [2¨C5]. So far, little is known about the IL-23/Th17 pathway in Chinese IBD patients, and many studies illustrate that genetic mutations that predispose to IBD appear to vary between different geographical and racial groups [6, 7]. Thus, our previous study examined the distribution of 26 SNPs of UC and 18 SNPs of CD in the IL-23/Th17 pathway genes in Chinese IBD patients and found that the polymorphisms of IL-12B, IL23R, JAK2, and TNFSF15 are strongly associated with Chinese IBD patients. It is illustrated that the IL-23/Th17 pathway is a key regulator of intestinal homeostasis and proinflammatory response in defense of microbial infection [8¨C10]. IL-12B encodes the IL-12p40 subunit shared by IL-12 and IL-23 cytokine on the genetic level
%U http://www.hindawi.com/journals/mi/2013/425915/