Expression of Interleukin-26 is upregulated in inflammatory bowel disease

Makoto Fujii; Atsushi Nishida; Hirotsugu Imaeda; Masashi Ohno; Kyohei Nishino; Shigeki Sakai; Osamu Inatomi; Shigeki Bamba; Masahiro Kawahara; Tomoharu Shimizu; Akira Andoh

doi:10.3748/wjg.v23.i30.5519

Expression of Interleukin-26 is upregulated in inflammatory bowel disease

World J Gastroenterol. 2017 Aug 14;23(30):5519-5529. doi: 10.3748/wjg.v23.i30.5519.

Affiliation

¹ Makoto Fujii, Atsushi Nishida, Hirotsugu Imaeda, Masashi Ohno, Kyohei Nishino, Shigeki Sakai, Osamu Inatomi, Shigeki Bamba, Masahiro Kawahara, Akira Andoh, Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.

Abstract

Aim: To investigate interleukin (IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and the function of IL-26.

Methods: Human colonic subepithelial myofibroblasts (SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by real-time polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering (si) RNA transfection.

Results: The mRNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the mRNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and siRNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the mRNA expression of IL-6 and IL-8 induced by IL-26.

Conclusion: These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.

Keywords: Inflammatory bowel disease; Interleukin-26; Myofibroblasts.

MeSH terms

Biopsy
Colitis, Ulcerative / pathology*
Colitis, Ulcerative / surgery
Colon / cytology
Colon / pathology*
Crohn Disease / pathology*
Crohn Disease / surgery
Humans
Immunohistochemistry
Interleukin-6 / metabolism
Interleukin-8 / metabolism
Interleukins / metabolism*
Intestinal Mucosa / cytology
Intestinal Mucosa / pathology*
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Myofibroblasts
NF-kappa B / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors
Primary Cell Culture
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Real-Time Polymerase Chain Reaction
STAT1 Transcription Factor / genetics
STAT1 Transcription Factor / metabolism
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Signal Transduction
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism
Up-Regulation

Substances

CXCL8 protein, human
IL26 protein, human
IL6 protein, human
Interleukin-6
Interleukin-8
Interleukins
NF-kappa B
Phosphoinositide-3 Kinase Inhibitors
RNA, Messenger
RNA, Small Interfering
STAT1 Transcription Factor
STAT1 protein, human
STAT3 Transcription Factor
STAT3 protein, human
Transcription Factor AP-1
Mitogen-Activated Protein Kinases