期刊
PLOS ONE
卷 8, 期 3, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0057955
关键词
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资金
- National Science Council, Taiwan [NSC101-2314-B-182A-112, NSC98-2321-B-182-004, NSC99-2321-B-182-003, NSC98-2320-B-182-004-MY3, NSC98-2314-B-182-021-MY3]
- Ministry of Education, Taiwan [EMRPD1B0311, EMRPD1B0321]
- Chang Gung Medical Research Foundation, Taiwan [CMRPG391032, CMRPG381522, CMRPD170493, CMRPD180373, CMRPD1A0151, CMRPD1B0381, CMRPG3B1091]
Interleukin-1 beta (IL-1 beta) plays a critical mediator in the pathogenesis of eye diseases. The implication of IL-1 beta 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-1 beta-induced MMP-9 expression in Statens Seruminstitut Rabbit Corneal Cells (SIRCs) are largely unclear. Here, we demonstrated that in SIRCs, IL-1 beta induced MMP-9 promoter activity and mRNA expression associated with an increase in the secretion of pro-MMP-9. IL-1 beta-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-kappa B (Bay11-7082), or AP-1 (Tanshinone IIA) and transfection with siRNA of p42 or JNK2. Moreover, IL-1 beta markedly stimulated p42/p44 MAPK and JNK1/2 phosphorylation in SIRCs. In addition, IL-1 beta also enhanced p42/p44 MAPK translocation from the cytosol into the nucleus. On the other hand, IL-1 beta induced c-Jun and c-Fos mRNA expression, c-Jun phosphorylation, and AP-1 promoter activity. NF-kappa B translocation, I kappa B alpha degradation, and NF-kappa B promoter activity were also enhanced by IL-1 beta. Pretreatment with U0126 or SP600125 inhibited IL-1 beta-induced AP-1 and NF-kappa B promoter activity, but not NF-kappa B translocation from the cytosol into the nucleus. Finally, we established that IL-1 beta could stimulate SIRCs migration via p42/p44 MAPK-, JNK1/2-, AP-1-, and NF-kappa B-dependent MMP-9 induction. These results suggested that NF-kappa B and AP-1 activated by JNK1/2 and p42/p44 MAPK cascade are involved in IL-1 beta-induced MMP-9 expression in SIRCs.
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