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Src tyrosine kinases mediate crystalline silica-induced NF-κB activation through tyrosine phosphorylation of IκB-α and p65 NF-κB in rAW 264.7 macrophages
- Title
- Src tyrosine kinases mediate crystalline silica-induced NF-κB activation through tyrosine phosphorylation of IκB-α and p65 NF-κB in rAW 264.7 macrophages
- Authors
- Kang J.L.; Jung H.J.; Lee K.; Kim H.R.
- Ewha Authors
- 이지희; 김형래; 이경은
- SCOPUS Author ID
- 이지희; 김형래; 이경은
- Issue Date
- 2006
- Journal Title
- Toxicological Sciences
- ISSN
- 1096-6080
- Citation
- Toxicological Sciences vol. 90, no. 2, pp. 470 - 477
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Protein tyrosine kinases (PTKs) and mitogen-activated protein kinases (MAPKs) have been demonstrated to play a crucial role in the signaling pathways induced by silica. In the present study, we investigated whether Src family TKs play a role in crystalline silica-induced NF-κB activation and whether NF-κB activation requires Src TK-dependent MAPK activity in RAW 264.7 cells, a mouse peritoneal macrophage cell line. Selective Src TK inhibitors, damnacanthal or PP1, inhibited silica-induced NF-κB activation in a dose-dependent manner. Furthermore, these kinase inhibitors suppressed silica-induced tyrosine phosphorylation of IκB-α and p65 NF-κB. Within a similar time frame, c-Src and Lck were physically associated with IκB-α and with p65 NF-κB. Silica stimulated the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), but not p38 MAPK and c-Jun NH2-terminal kinase 1 and 2 (JNK1/2). Damnacanthal or PP1 substantially blocked the silica-induced activation of ERK1/2. Moreover, PD98059, an inhibitor of ERK1/2, or SB203580, an inhibitor of p38 MAPK, failed to inhibit silica-induced NF-κB activation. These results suggest that c-Src and Lck act for silica-induced NF-κB activation by mediating the tyrosine phosphorylations of IκB-α and p65 NF-κB. However, the Src TK-dependent activation of ERK1/2 may not be involved in the silica signaling pathway leading to NF-κB activation. © 2006 Oxford University Press.
- DOI
- 10.1093/toxsci/kfj096
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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