Cigarette smoke condensate enhances respiratory syncytial virus-induced chemokine release by modulating NF-kappa B and interferon regulatory factor activation.
Exposure to cigarette smoke is a risk factor contributing to the severity of respiratory tract infections associated with respiratory syncytial virus (RSV). Stimulation of airway epithelial cells by either RSV or cigarette smoke condensate (CSC) has been shown to induce secretion of the proinflammatory chemokines. However, the effect of coexposure of airway epithelial cells to CSC and RSV on inducible chemokine production has not been previously investigated. The results of this study indicate that CSC costimulation significantly increased RSV-induced interleukin-8 (IL-8) and monocyte chemoattactant protein-1 gene and protein expression when compared with each stimulus alone. Promoter deletion studies identified the interferon stimulatory response element (ISRE) of the IL-8 promoter as a critical region responsible for the synergistic increase of IL-8 gene transcription during mixed exposure. CSC costimulation enhanced RSV-induced activation of interferon regulatory factor (IRF)-1 and IRF-7, which bind to the ISRE site. CSC also furthered RSV-induced activation of the transcription factor nuclear factor kappa B (NF-kappaB), as shown by increased NF-kappaB DNA binding to its specific site of the IL-8 promoter and increased NF-kappaB-driven gene transcription. Therefore, our data demonstrate that a combined exposure to CSC and RSV synergistically increases chemokine expression in airway epithelial cells, suggesting that CSC contributes to an exuberant immune response to RSV by stimulating overlapping signal transduction pathways.
Castro
Shawn Monique
SM
Department of Pharmacology and Toxicology, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Kolli
Deepthi
D
Guerrero-Plata
Antonieta
A
Garofalo
Roberto P
RP
Casola
Antonella
A
D001483:Base Sequence; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D012906:Smoke; D014026:Nicotiana
D018925:Chemokines; D017931:DNA Primers; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D012906:Smoke