Interleukin-17A stimulates migration of periodontal ligament fibroblasts via p38 MAPK/NF-κB -dependent MMP-1 expression.
Interleukin-17 (IL-17) is a cytokine secreted predominantly by Th17 cells. Although IL-17 is primarily associated with the induction of tissue inflammation, the other biological functions of IL-17, including its wound-healing functions, have yet to be thoroughly explored. Fibroblast proliferation and migration play essential roles in periodontal wound-healing responses. In this study, we report that IL-17A can increase the migration and expression of matrix metalloproteinase (MMP)-1 in human periodontal ligament (PDL) fibroblasts but has no effect on PDL fibroblast proliferation. IL-17A-induced MMP-1 expression led to cell migration, which was attenuated by pre-treatment with IL-17 receptor neutralizing antibody and small interfering RNA (siRNA) for MMP-1. The IL-17A-induced cell migration was also attenuated by its tissue inhibitor of matrix metalloproteinase (TIMP)-1. In addition, a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) inhibited IL-17A-induced increase of the migration and MMP-1 upregulation of PDL fibroblasts. The involvement of p38 MAPK in IL-17A-induced MMP-1 expression and cell migration was further confirmed by transfection of p38α siRNA. A nuclear factor kappaB (NF-κB) inhibitor (pyrrolidine dithiocarbamate) also suppressed the cell migration and MMP-1 expression enhanced by IL-17A. Moreover, transfection with p38α siRNA inhibited IL-17A-induced NF-κB nuclear translocation as well as NF-κB binding activity. Our results suggest that IL-17A enhances the migration of PDL fibroblasts by increasing MMP-1 expression through the IL-17 receptor, p38 MAPK, and NF-κB signal transduction pathways.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Yan
Y
Wu
Lingxin
L
Zhu
Lingshuang
L
Liu
Jie
J
Zhang
Bin
B
Peng
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014162:Transfection
D020381:Interleukin-17; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D048308:Mitogen-Activated Protein Kinase 14; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1