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
Version of Record online: 20 FEB 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 211, Issue 3, pages 759–770, June 2007
How to Cite
Liang, K.-C., Lee, C.-W., Lin, W.-N., Lin, C.-C., Wu, C.-B., Luo, S.-F. and Yang, C.-M. (2007), 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. J. Cell. Physiol., 211: 759–770. doi: 10.1002/jcp.20992
- Issue online: 27 MAR 2007
- Version of Record online: 20 FEB 2007
- Manuscript Accepted: 16 NOV 2006
- Manuscript Received: 17 APR 2006
- National Science Council, Taiwan. Grant Number: NSC94-2320-B-182-037
- Chang Gung Medical Research Foundation. Grant Number: CMRPD-32043
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.