Article: article d'un périodique ou d'un magazine.
Exaggerated IL-8 and IL-6 responses to TNF-alpha by parainfluenza virus type 4-infected NCI-H292 cells.
American Journal of Physiology. Lung Cellular and Molecular Physiology
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Publication types: Journal Article
Respiratory viruses induce and potentiate airway inflammation, which is related to the induction of proinflammatory mediators such as interleukin (IL)-8 and IL-6. Here we report on mechanisms implicated in IL-8 and IL-6 production by airway epithelium-like NCI-H292 cells exposed to parainfluenza virus type 4a (PIV-4). PIV-4 readily infected NCI-H292 cells as reflected by intracellular PIV-4 antigen expression. PIV-4 infection triggered a biphasic IL-8 and IL-6 mRNA response. Transient transfection with truncated and mutated promoter constructs identified NF-kappaB and activator protein (AP)-1, and CCAAT-enhancer binding protein (C/EBP) as the relevant transcription factors for PIV-4-induced IL-8 and IL-6 gene transcription, respectively. An increase of DNA-binding activities for NF-kappaB and C/EBP paralleled the induction of the first and second IL-8 and IL-6 mRNA peaks, whereas the onset of AP-1 paralleled the first IL-8 mRNA peak only. The second mRNA peak, apparently dependent on viral replication, coincided also with a marked reduction of IL-8 and IL-6 mRNA degradation. Importantly, cells at the time of the reduced mRNA degradation displayed an exaggerated IL-8 and IL-6 protein production to a secondary stimulus, as exemplified by steeper dose-response curves to TNF-alpha. Thus PIV-4 infection enhances epithelial IL-8 and IL-6 production by transcriptional and posttranscriptional mechanisms. The previously unrecognized phase of reduced IL-8 and IL-6 mRNA degradation and the concurrent amplified epithelial IL-8 and IL-6 responses may play an important role in virus-induced potentiation of airway inflammation.
Adenocarcinoma, Antineoplastic Agents/pharmacology, CCAAT-Enhancer-Binding Proteins/metabolism, Carcinoma, Mucoepidermoid, Cell Line, Tumor, Humans, Interleukin-6/genetics, Interleukin-6/metabolism, Interleukin-8/genetics, Interleukin-8/metabolism, Lung Neoplasms, NF-kappa B/metabolism, Parainfluenza Virus 4, Human, Promoter Regions, Genetic/physiology, RNA, Messenger/analysis, Rubulavirus Infections/immunology, Rubulavirus Infections/metabolism, Transcription Factor AP-1/metabolism, Tumor Necrosis Factor-alpha/pharmacology
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