Interleukin‐25 regulates matrix metalloproteinase‐2 and ‐9 expression in periodontal fibroblast cells through ERK and P38MAPK pathways

Abstract Interleukin‐25 (IL‐25) has been recognized as a new member of the IL‐17 family and implicated in various inflammatory pathology. We aimed to investigate the effects of IL‐25 on the expression of matrix metalloproteinase‐2 (MMP‐2), MMP‐8, and MMP‐9 in periodontal fibroblast cells (PFCs), cell migration, cytoskeleton F‐actin, and to explore the involved extracellular‐regulated protein kinases (ERKs), P38 mitogen‐activated protein kinase (P38MAPK) signaling pathways, and IL‐17 receptor. To evaluate the expression of MMP‐2, MMP‐8, MMP‐9, and F‐actin, PFCs were treated by various doses of IL‐25 (0, 20, 50, 100, and 500 ng/ml). Protein expression of extracellular metalloproteinase inducer (EMMPRIN) was also evaluated by western blot. Cell scratches experiment was performed to test the cell migration ability. ERK, P38MAPK, and Jun N‐terminal kinase signal pathways and related expression of P‐ERK and P‐P38MAPK were examined after treatment of different doses of IL‐25 and after treatment of inhibitors of ERK and P38MAPK. Immunofluorescence of MMP‐2, MMP‐9, and F‐actin were evaluated after inhibitor treatment. IL‐17RB small interfering RNA was used to examine the receptor of IL‐25. IL‐25 increased the protein expression of MMP‐2 and MMP‐9. MMP‐8 and EMMPRIN expressions were not regulated by IL‐25 in PFCs. Positive IF staining extended strongly from the central part to the whole cell. IL‐25 mediated MMP‐2, MMP‐9, F‐actin expressions and cell migration were regulated by P38MAPK and ERK pathways, and IL‐17RB. SB203580 and U0126 blocked the effects of IL‐25 through the inhibition of ERK, P38MAPK, P‐ERK, and P‐P38MAPK. The data indicate that IL‐25 could regulate cell migration, MMP‐2, and MMP‐9 expression, but not MMP‐8 expression, in PFCs. Moreover, the regulation effects were involved in ERK and P38MAPK pathways, and receptor IL‐17RB.