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TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways.
J Cell Physiol. 2010 Aug; 224(2):454-64.JC

Abstract

Matrix metalloproteinases (MMPs), in particular MMP-9, have been shown to be induced by cytokines, including TNF-alpha and contributes to airway inflammation. However, the mechanisms underlying TNF-alpha-induced MMP-9 expression in human A549 cells remain unclear. Here, we report that TNF-alpha-induced MMP-9 gene expression was mediated through the TNFR1/TRAF2/PKCalpha-dependent signaling pathways in A549 cells, determined by zymographic, RT-PCR, and Western blotting analyses. TNF-alpha-induced MMP-9 expression was reduced by pretreatment with a TNFR Ab. Furthermore, TNF-alpha-induced TNFR1 and TRAF2 complex formation was revealed by immunoprecipitation using an anti-TNFR1 Ab followed by Western blot analysis against an anti-TRAF2 or anti-TNFR1 Ab. In addition, TNF-alpha-induced MMP-9 expression was also reduced by pretreatment with the inhibitor of PKCalpha (Gö6983), c-Src (PP1), EGFR (AG1478), or PI3K (LY294002) or transfection with siRNAs of PKCalpha, Src, EGFR, Akt, p65, p300, and c-Jun. On the other hand, TNF-alpha stimulated the phosphorylation of c-Src, EGFR, Akt, JNK1/2, and c-Jun, which were inhibited by pretreatment with Gö6983. We also showed that TNF-alpha induced Akt translocation and the formation of an Akt/p65/p300 complex. Pretreatment with the inhibitor of JNK1/2 (SP600125) but not the inhibitor of MEK1/2 (U0126), p38 MAPK (SB202190), or PI3K (LY294002), markedly inhibited TNF-alpha-induced c-Jun mRNA levels. Taken together, these data suggest that in A549 cells, TNF-alpha induces MMP-9 expression via the TNFR1/TRAF2/PKCalpha-dependent JNK1/2/c-Jun and c-Src/EGFR/PI3K/Akt pathways.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.No 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

20333651

Citation

Lee, I-Ta, et al. "TNF-alpha Induces Matrix Metalloproteinase-9 Expression in A549 Cells: Role of TNFR1/TRAF2/PKCalpha-dependent Signaling Pathways." Journal of Cellular Physiology, vol. 224, no. 2, 2010, pp. 454-64.
Lee IT, Lin CC, Wu YC, et al. TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways. J Cell Physiol. 2010;224(2):454-64.
Lee, I. T., Lin, C. C., Wu, Y. C., & Yang, C. M. (2010). TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways. Journal of Cellular Physiology, 224(2), 454-64. https://doi.org/10.1002/jcp.22142
Lee IT, et al. TNF-alpha Induces Matrix Metalloproteinase-9 Expression in A549 Cells: Role of TNFR1/TRAF2/PKCalpha-dependent Signaling Pathways. J Cell Physiol. 2010;224(2):454-64. PubMed PMID: 20333651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways. AU - Lee,I-Ta, AU - Lin,Chih-Chung, AU - Wu,Yang-Chang, AU - Yang,Chuen-Mao, PY - 2010/3/25/entrez PY - 2010/3/25/pubmed PY - 2010/6/17/medline SP - 454 EP - 64 JF - Journal of cellular physiology JO - J Cell Physiol VL - 224 IS - 2 N2 - Matrix metalloproteinases (MMPs), in particular MMP-9, have been shown to be induced by cytokines, including TNF-alpha and contributes to airway inflammation. However, the mechanisms underlying TNF-alpha-induced MMP-9 expression in human A549 cells remain unclear. Here, we report that TNF-alpha-induced MMP-9 gene expression was mediated through the TNFR1/TRAF2/PKCalpha-dependent signaling pathways in A549 cells, determined by zymographic, RT-PCR, and Western blotting analyses. TNF-alpha-induced MMP-9 expression was reduced by pretreatment with a TNFR Ab. Furthermore, TNF-alpha-induced TNFR1 and TRAF2 complex formation was revealed by immunoprecipitation using an anti-TNFR1 Ab followed by Western blot analysis against an anti-TRAF2 or anti-TNFR1 Ab. In addition, TNF-alpha-induced MMP-9 expression was also reduced by pretreatment with the inhibitor of PKCalpha (Gö6983), c-Src (PP1), EGFR (AG1478), or PI3K (LY294002) or transfection with siRNAs of PKCalpha, Src, EGFR, Akt, p65, p300, and c-Jun. On the other hand, TNF-alpha stimulated the phosphorylation of c-Src, EGFR, Akt, JNK1/2, and c-Jun, which were inhibited by pretreatment with Gö6983. We also showed that TNF-alpha induced Akt translocation and the formation of an Akt/p65/p300 complex. Pretreatment with the inhibitor of JNK1/2 (SP600125) but not the inhibitor of MEK1/2 (U0126), p38 MAPK (SB202190), or PI3K (LY294002), markedly inhibited TNF-alpha-induced c-Jun mRNA levels. Taken together, these data suggest that in A549 cells, TNF-alpha induces MMP-9 expression via the TNFR1/TRAF2/PKCalpha-dependent JNK1/2/c-Jun and c-Src/EGFR/PI3K/Akt pathways. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/20333651/TNF_alpha_induces_matrix_metalloproteinase_9_expression_in_A549_cells:_role_of_TNFR1/TRAF2/PKCalpha_dependent_signaling_pathways_ L2 - https://doi.org/10.1002/jcp.22142 DB - PRIME DP - Unbound Medicine ER -