Interleukin-31 stimulates production of inflammatory mediators from human colonic subepithelial myofibroblasts.
Interleukin (IL)-31 is mainly produced by CD4+ T cells, in particular T cells skewed toward a Th2 phenotype. Here we report for the first time that IL-31 stimulates secretion of proinflammatory cytokines, chemokines and matrix metalloproteinases (MMPs) from human colonic subepithelial myofibroblasts (SEMFs). The effects of IL-31 were investigated by cDNA microarrays, enzyme-linked immunosorbent assay, and real-time PCR. IL-31 effectively induced chemokines [IL-8, GRO-alpha (growth-related oncogene-alpha), MCP-3 (monocyte chemoattractant protein-3), CXCL3, CCL13 and CCL15], proinflammatory cytokines (IL-6, IL-16 and IL-32) and matrix metalloproteinases (MMP-1, MMP-3, MMP-25 and MMP-7). IL-31 dose-dependently induced secretion of IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3. The effects of IL-31 were comparable to the effects of IL-17A. IL-31 and IL-17A showed additive effects on IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3 secretion. In conclusion, we demonstrated that IL-31 is a potent inducer of proinflammatory mediators in human colonic SEMFs. IL-31 may function as a proinflammatory cytokine derived from Th2 cells.
Yagi
Yuhki
Y
Department of Internal Medicine, Shiga University of Medical Science, Otsu 520-2192, Japan.
Andoh
Akira
A
Nishida
Atsushi
A
Shioya
Makoto
M
Nishimura
Takashi
T
Hashimoto
Takayoshi
T
Tsujikawa
Tomoyuki
T
Saito
Yasuharu
Y
Fujiyama
Yoshihide
Y
D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D032390:Myoblasts, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018418:Th2 Cells / Q000378:metabolism
D016207:Cytokines; D004338:Drug Combinations; C502187:IL31 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D007378:Interleukins; D020782:Matrix Metalloproteinases