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
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Biopsy
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Colitis, Ulcerative / pathology*
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Colitis, Ulcerative / surgery
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Colon / cytology
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Colon / pathology*
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Crohn Disease / pathology*
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Crohn Disease / surgery
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Humans
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Immunohistochemistry
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Interleukin-6 / metabolism
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Interleukin-8 / metabolism
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Interleukins / metabolism*
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Intestinal Mucosa / cytology
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Intestinal Mucosa / pathology*
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Myofibroblasts
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Primary Cell Culture
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Real-Time Polymerase Chain Reaction
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / metabolism
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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Up-Regulation
Substances
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CXCL8 protein, human
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IL26 protein, human
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IL6 protein, human
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Interleukin-6
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Interleukin-8
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Interleukins
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NF-kappa B
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Phosphoinositide-3 Kinase Inhibitors
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RNA, Messenger
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RNA, Small Interfering
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STAT1 Transcription Factor
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STAT1 protein, human
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STAT3 Transcription Factor
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STAT3 protein, human
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Transcription Factor AP-1
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Mitogen-Activated Protein Kinases