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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 PublicationJournal of Immunology
ISSN00221767
Volume160Issue:6Pages:3038-3045
AbstractRecent 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.
URLView the original
Language英語
Fulltext Access
Document TypeJournal article
CollectionUniversity of Macau
AffiliationScripps 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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