High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease

Fengming Yi,Bing Xia,Shufang Xu,Lu Song,Sha Huang,Feng Zhou,Xiaobing Wang,Rui Zhou,Wei Wang

doi:10.1155/2013/425915

Fengming Yi, Bing Xia + Show 7 more

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https://doi.org/10.1155/2013/425915

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Abstract

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.

Highlights

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract which includes ulcerative colitis (UC) and Crohn’s disease (CD)
We found that IL-12B and TNFSF15 genes polymorphisms were associated with UC in Chinese patients, which clearly showed that these two genes were involved in human susceptibility to UC
The results indicated that UC patients had higher mRNA and serum levels of IL-12B and tumor necrosis factor-like cytokine 1A (TL1A), while Janus kinase 2 gene (JAK2) and IL-23R levels were higher in UC and CD patients

Summary

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). 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 interleukin23/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) [2,3,4,5]. The proinflammatory cytokines IL-12 and IL-23 play critical roles in bridging the innate and adaptive immune systems in IBD, while IL-23R may play more important role than IL-12/23p40 in the genetic susceptibility to IBD [8, 12, 13]

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