IL-1β promotes A549 cell migration via MAPKs/AP-1- and NF-κB-dependent matrix metalloproteinase-9 expression

Chih Chung Lin, Chang Ting Kuo, Ching Yi Cheng, Cheng Ying Wu, Chiang Wen Lee, Hsi Lung Hsieh, I-Ta Lee, Chuen Mao Yang

Research output: Contribution to journalArticle

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Abstract

Matrix metalloproteinases (MMPs), in particular MMP-9, is induced by cytokines including IL-1β and contributes to airway injury and remodeling. However, the mechanisms underlying IL-1β-induced MMP-9 expression and cell migration in human A549 cells remain unclear. Here, we report that the IL-1β-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-1β-induced responses was further ensured by transfection with siRNA of MEK1, p42, p38, or JNK2. Moreover, the IL-1β-induced MMP-9 gene expression was also mediated through the translocation of NF-κB (p65) into the nucleus and the degradation of IκBα. In addition, the IL-1β-induced c-Jun phosphorylation was reduced by pretreatment with U0126 or SP600125. IL-1β 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-1β had no effect on the cells transfected with a NF-κB-mutated MMP-9 promoter construct, suggesting that NF-κB is required for this response. Finally, the IL-1β-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-κB, and AP-1 are essential for the IL-1β-induced MMP-9 gene expression and cell migration.

Original languageEnglish
Pages (from-to)1652-1662
Number of pages11
JournalCellular Signalling
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 1 2009
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Transcription Factor AP-1
Interleukin-1
Cell Movement
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Gene Expression
A549 Cells
Airway Remodeling
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Small Interfering RNA
Transfection
Western Blotting
Phosphorylation
Cytokines
Polymerase Chain Reaction

Keywords

  • Cytokines
  • Matrix metalloproteinases
  • Mitogen-activated protein kinases
  • Pulmonary epithelial cells
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lin, C. C., Kuo, C. T., Cheng, C. Y., Wu, C. Y., Lee, C. W., Hsieh, H. L., ... Yang, C. M. (2009). IL-1β promotes A549 cell migration via MAPKs/AP-1- and NF-κB-dependent matrix metalloproteinase-9 expression. Cellular Signalling, 21(11), 1652-1662. https://doi.org/10.1016/j.cellsig.2009.07.002

IL-1β promotes A549 cell migration via MAPKs/AP-1- and NF-κB-dependent matrix metalloproteinase-9 expression. / Lin, Chih Chung; Kuo, Chang Ting; Cheng, Ching Yi; Wu, Cheng Ying; Lee, Chiang Wen; Hsieh, Hsi Lung; Lee, I-Ta; Yang, Chuen Mao.

In: Cellular Signalling, Vol. 21, No. 11, 01.11.2009, p. 1652-1662.

Research output: Contribution to journalArticle

Lin, Chih Chung ; Kuo, Chang Ting ; Cheng, Ching Yi ; Wu, Cheng Ying ; Lee, Chiang Wen ; Hsieh, Hsi Lung ; Lee, I-Ta ; Yang, Chuen Mao. / IL-1β promotes A549 cell migration via MAPKs/AP-1- and NF-κB-dependent matrix metalloproteinase-9 expression. In: Cellular Signalling. 2009 ; Vol. 21, No. 11. pp. 1652-1662.
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