Interleukin-1β induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-κB signaling pathways in human tracheal smooth muscle cells

✍ Scribed by Kao-Chih Liang; Chiang-Wen Lee; Wei-Ning Lin; Chih-Chung Lin; Chou-Bin Wu; Shue-Fen Luo; Chuen-Mao Yang

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 593 KB
• Volume: 211
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20992

✦ Synopsis

Abstract

Matrix metalloproteinases (MMPs) are responsible for degradation of extracellular matrix and play important roles in cell migration, proliferation, and tissue remodeling related to airway inflammation. Interleukin‐1β (IL‐1β) has been shown to induce MMP‐9 production in many cell types and contribute to airway inflammatory responses. However, the mechanisms underlying MMP‐9 expression induced by IL‐1β in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here, we investigated the roles of p42/p44 MAPK, p38 MAPK, JNK, and NF‐κB pathways for IL‐1β‐induced MMP‐9 production in HTSMCs. IL‐1β induced production of MMP‐9 protein and mRNA in a time‐ and concentration‐dependent manner determined by zymographic, Western blotting, and RT‐PCR analyses, which was attenuated by inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), JNK (SP600125), and NF‐κB (helenalin), and transfection with dominant negative mutants of MEK1/2, p38 and JNK, respectively. IL‐1β‐stimulated phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK was attenuated by pretreatment with U0126, SB202190, SP600125, or transfection with these dominant negative mutants of MEK, ERK, p38 and JNK, respectively. Furthermore, IL‐1β‐stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α was blocked by helenalin. Finally, the reporter gene assay revealed that MAPKs and NF‐κB are required for IL‐1β‐induced MMP‐9 luciferase activity in HTSMCs. MMP‐9 promoter activity was enhanced by IL‐1β in HTSMCs transfected with MMP‐9‐Luc, which was inhibited by helenalin, U0126, SB202190, and SP600125. Taken together, the transcription factor NF‐κB, p42/p44 MAPK, p38 MAPK, and JNK that are involved in MMP‐9 expression in HTSMCs exposed to IL‐1β have now been identified. J. Cell. Physiol. 211: 759–770, 2007. © 2007 Wiley‐Liss, Inc.