Role of the Rho GTPase in bradykinin-stimulated nuclear factor-κb activation and IL-1β gene expression in cultured human epithelial cells

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	Role of the Rho GTPase in bradykinin-stimulated nuclear factor-κb activation and IL-1β gene expression in cultured human epithelial cells
	Pan Z.K.; Ye R.D.; Christiansen S.C.; Jagels M.A.; Bokoch G.M.; Zuraw B.L.
	1998-03-15
Source Publication	Journal of Immunology
ISSN	00221767
Volume	160 Issue:6 Pages:3038-3045
Abstract	Recent evidence suggests a novel role of bradykinin (BK) in stimulating gene transcription. This study examined the effect of BK on nuclear factor κB (NF-κB) activation and IL-1β synthesis in human epithelial cells. Stimulation of A549 cells and primary bronchial epithelial cells with BK rapidly activated NF-κB. BK also increased the level of secreted immunoreactive IL-1β in A549 culture supernatants, an effect that was blocked by actinomycin D and the B2 BK receptor antagonist HOE-140. The role of NF-κB activation in BK-induced IL-1β synthesis was demonstrated by the ability of BK to stimulate increased chloramphenicol acetyltransferase (CAT) activity in A549 cells transfected with a reporter plasmid containing three κB enhancers from the IL-1β gene, while deletion of the κB enhancer sequences eliminated BK-stimulated CAT activity. C3 transferase exoenzyme, an inhibitor of Rho, abolished BK-induced NF-κB activation at 10 μg/ml and significantly inhibited BK-stimulated IL-1β synthesis at 5 μg/ml. A dominant-negative form of RhoA (T19N) inhibited BK-stimulated reporter gene expression in a dose-dependent and κB-dependent manner. Cotransfection of A549 cells with an expression vector encoding a constitutively active form of RhoA (Q63L) along with the IL-1β promoter-CAT reporter plasmid resulted in a marked increase in NF-κB activity compared with transfection with the IL- 1β promoter-CAT reporter plasmid alone. These results demonstrate that BK stimulates NF-κB activation and IL-1β synthesis in A549 cells, and that RhoA is both necessary and sufficient to mediate this effect.
URL	View the original
Language	英語English
Fulltext Access	View Full-Text via Scopus
Document Type	Journal article
Collection	University of Macau
Affiliation	Scripps Research Institute
Recommended Citation GB/T 7714	Pan Z.K.,Ye R.D.,Christiansen S.C.,et al. Role of the Rho GTPase in bradykinin-stimulated nuclear factor-κb activation and IL-1β gene expression in cultured human epithelial cells[J]. Journal of Immunology, 1998, 160(6), 3038-3045.
APA	Pan Z.K.., Ye R.D.., Christiansen S.C.., Jagels M.A.., Bokoch G.M.., & Zuraw B.L. (1998). Role of the Rho GTPase in bradykinin-stimulated nuclear factor-κb activation and IL-1β gene expression in cultured human epithelial cells. Journal of Immunology, 160(6), 3038-3045.
MLA	Pan Z.K.,et al."Role of the Rho GTPase in bradykinin-stimulated nuclear factor-κb activation and IL-1β gene expression in cultured human epithelial cells".Journal of Immunology 160.6(1998):3038-3045.

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