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IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression.
Cell Signal 2009; 21(11):1652-62CS

Abstract

Matrix metalloproteinases (MMPs), in particular MMP-9, is induced by cytokines including IL-1 beta and contributes to airway injury and remodeling. However, the mechanisms underlying IL-1 beta-induced MMP-9 expression and cell migration in human A549 cells remain unclear. Here, we report that the IL-1 beta-induced MMP-9 gene expression was mediated through the activation of p42/p44 MAPK, p38 MAPK, and JNK1/2 in A549 cells, determined by zymographic, RT-PCR, and Western blotting. The involvement of MAPKs in the IL-1beta-induced responses was further ensured by transfection with siRNA of MEK1, p42, p38, or JNK2. Moreover, the IL-1 beta-induced MMP-9 gene expression was also mediated through the translocation of NF-kappaB (p65) into the nucleus and the degradation of I kappaB alpha. In addition, the IL-1 beta-induced c-Jun phosphorylation was reduced by pretreatment with U0126 or SP600125. IL-1 beta stimulated the transcriptional activity of wild-type MMP-9 promoter in A549 cells, which was inhibited by U0126, SB203580, SP600125, and helenalin. In contrast, IL-1 beta had no effect on the cells transfected with a NF-kappaB-mutated MMP-9 promoter construct, suggesting that NF-kappaB is required for this response. Finally, the IL-1 beta-induced MMP-9 expression led to cell migration which was attenuated by pretreatment with U0126, SB203580, SP600125, helenalin, or MMP-2/9 inhibitor. These results suggested that in A549 cells, the activation of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-kappaB, and AP-1 are essential for the IL-1 beta-induced MMP-9 gene expression and cell migration.

Authors+Show Affiliations

Department of Anesthetics, Chang Gung University and Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19616091

Citation

Lin, Chih-Chung, et al. "IL-1 Beta Promotes A549 Cell Migration Via MAPKs/AP-1- and NF-kappaB-dependent Matrix Metalloproteinase-9 Expression." Cellular Signalling, vol. 21, no. 11, 2009, pp. 1652-62.
Lin CC, Kuo CT, Cheng CY, et al. IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression. Cell Signal. 2009;21(11):1652-62.
Lin, C. C., Kuo, C. T., Cheng, C. Y., Wu, C. Y., Lee, C. W., Hsieh, H. L., ... Yang, C. M. (2009). IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression. Cellular Signalling, 21(11), pp. 1652-62. doi:10.1016/j.cellsig.2009.07.002.
Lin CC, et al. IL-1 Beta Promotes A549 Cell Migration Via MAPKs/AP-1- and NF-kappaB-dependent Matrix Metalloproteinase-9 Expression. Cell Signal. 2009;21(11):1652-62. PubMed PMID: 19616091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression. AU - Lin,Chih-Chung, AU - Kuo,Chang-Ting, AU - Cheng,Ching-Yi, AU - Wu,Cheng-Ying, AU - Lee,Chiang-Wen, AU - Hsieh,Hsi-Lung, AU - Lee,I-Ta, AU - Yang,Chuen-Mao, Y1 - 2009/07/16/ PY - 2009/06/16/received PY - 2009/07/08/accepted PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2009/11/7/medline SP - 1652 EP - 62 JF - Cellular signalling JO - Cell. Signal. VL - 21 IS - 11 N2 - Matrix metalloproteinases (MMPs), in particular MMP-9, is induced by cytokines including IL-1 beta and contributes to airway injury and remodeling. However, the mechanisms underlying IL-1 beta-induced MMP-9 expression and cell migration in human A549 cells remain unclear. Here, we report that the IL-1 beta-induced MMP-9 gene expression was mediated through the activation of p42/p44 MAPK, p38 MAPK, and JNK1/2 in A549 cells, determined by zymographic, RT-PCR, and Western blotting. The involvement of MAPKs in the IL-1beta-induced responses was further ensured by transfection with siRNA of MEK1, p42, p38, or JNK2. Moreover, the IL-1 beta-induced MMP-9 gene expression was also mediated through the translocation of NF-kappaB (p65) into the nucleus and the degradation of I kappaB alpha. In addition, the IL-1 beta-induced c-Jun phosphorylation was reduced by pretreatment with U0126 or SP600125. IL-1 beta stimulated the transcriptional activity of wild-type MMP-9 promoter in A549 cells, which was inhibited by U0126, SB203580, SP600125, and helenalin. In contrast, IL-1 beta had no effect on the cells transfected with a NF-kappaB-mutated MMP-9 promoter construct, suggesting that NF-kappaB is required for this response. Finally, the IL-1 beta-induced MMP-9 expression led to cell migration which was attenuated by pretreatment with U0126, SB203580, SP600125, helenalin, or MMP-2/9 inhibitor. These results suggested that in A549 cells, the activation of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-kappaB, and AP-1 are essential for the IL-1 beta-induced MMP-9 gene expression and cell migration. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/19616091/IL_1_beta_promotes_A549_cell_migration_via_MAPKs/AP_1__and_NF_kappaB_dependent_matrix_metalloproteinase_9_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(09)00209-5 DB - PRIME DP - Unbound Medicine ER -