IL-1β Promotes Corneal Epithelial Cell Migration by Increasing MMP-9 Expression through NF-κB- and AP-1-Dependent Pathways

Hui Ching Tseng, I-Ta Lee, Chih Chung Lin, Pei Ling Chi, Shin Ei Cheng, Ruey Horng Shih, Li Der Hsiao, Chuen Mao Yang

Research output: Contribution to journalArticle

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Abstract

Interleukin-1β (IL-1β) plays a critical mediator in the pathogenesis of eye diseases. The implication of IL-1β in inflammatory responses has been shown to be mediated through up-regulation of inflammatory genes, including matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of IL-1β-induced MMP-9 expression in Statens Seruminstitut Rabbit Corneal Cells (SIRCs) are largely unclear. Here, we demonstrated that in SIRCs, IL-1β induced MMP-9 promoter activity and mRNA expression associated with an increase in the secretion of pro-MMP-9. IL-1β-induced pro-MMP-9 expression and MMP-9 mRNA levels were attenuated by pretreatment with the inhibitor of MEK1/2 (U0126), JNK1/2 (SP600125), NF-κB (Bay11-7082), or AP-1 (Tanshinone IIA) and transfection with siRNA of p42 or JNK2. Moreover, IL-1β markedly stimulated p42/p44 MAPK and JNK1/2 phosphorylation in SIRCs. In addition, IL-1β also enhanced p42/p44 MAPK translocation from the cytosol into the nucleus. On the other hand, IL-1β induced c-Jun and c-Fos mRNA expression, c-Jun phosphorylation, and AP-1 promoter activity. NF-κB translocation, IκBα degradation, and NF-κB promoter activity were also enhanced by IL-1β. Pretreatment with U0126 or SP600125 inhibited IL-1β-induced AP-1 and NF-κB promoter activity, but not NF-κB translocation from the cytosol into the nucleus. Finally, we established that IL-1β could stimulate SIRCs migration via p42/p44 MAPK-, JNK1/2-, AP-1-, and NF-κB-dependent MMP-9 induction. These results suggested that NF-κB and AP-1 activated by JNK1/2 and p42/p44 MAPK cascade are involved in IL-1β-induced MMP-9 expression in SIRCs.

Original languageEnglish
Article numbere57955
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 7 2013
Externally publishedYes

Fingerprint

gelatinase B
Matrix Metalloproteinase 9
Transcription Factor AP-1
interleukin-1
Interleukin-1
cell movement
Cell Movement
epithelial cells
Epithelial Cells
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
rabbits
Rabbits
promoter regions
Phosphorylation
cytosol
Cytosol
Messenger RNA
phosphorylation
pretreatment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

IL-1β Promotes Corneal Epithelial Cell Migration by Increasing MMP-9 Expression through NF-κB- and AP-1-Dependent Pathways. / Tseng, Hui Ching; Lee, I-Ta; Lin, Chih Chung; Chi, Pei Ling; Cheng, Shin Ei; Shih, Ruey Horng; Hsiao, Li Der; Yang, Chuen Mao.

In: PLoS One, Vol. 8, No. 3, e57955, 07.03.2013.

Research output: Contribution to journalArticle

Tseng, Hui Ching ; Lee, I-Ta ; Lin, Chih Chung ; Chi, Pei Ling ; Cheng, Shin Ei ; Shih, Ruey Horng ; Hsiao, Li Der ; Yang, Chuen Mao. / IL-1β Promotes Corneal Epithelial Cell Migration by Increasing MMP-9 Expression through NF-κB- and AP-1-Dependent Pathways. In: PLoS One. 2013 ; Vol. 8, No. 3.
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AU - Chi, Pei Ling

AU - Cheng, Shin Ei

AU - Shih, Ruey Horng

AU - Hsiao, Li Der

AU - Yang, Chuen Mao

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