Interleukin‐17A Stimulates Migration of Periodontal Ligament Fibroblasts Via p38 MAPK/NF‐κB ‐Dependent MMP‐1 Expression

Abstract 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. J. Cell. Physiol. 229: 292–299, 2014. © 2013 Wiley Periodicals, Inc.