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ABSTRACT: Background
Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36? and IL-36? using human colonic subepithelial myofibroblasts (SEMFs).Methods
The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-?B p65.Results
IL-36? and IL-36? significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36?/? and IL-17A or of IL-36?/? and tumor necrosis factor-? showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36? and/or IL-36? was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases and siRNAs specific for NF-?Bp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36? and/or IL-36?.Conclusion
These results suggest that IL-36? and IL-36? contribute to gut inflammation through the induction of proinflammatory mediators.
SUBMITTER: Kanda T
PROVIDER: S-EPMC4585048 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Kanda Toshihiro T Nishida Atsushi A Takahashi Kenichiro K Hidaka Kentaro K Imaeda Hirotsugu H Inatomi Osamu O Bamba Shigeki S Sugimoto Mitsushige M Andoh Akira A
Frontiers in medicine 20150922
<h4>Background</h4>Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36γ using human colonic subepithelial myofibroblasts (SEMFs).<h4>Methods</h4>The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reac ...[more]