title: Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.
abstract: The mechanisms of virus-induced enhancement of intercellular adhesion molecule-1 (ICAM-1) expression in epithelial cells are unknown. In the present study, the effect of respiratory syncytial virus (RSV) infection on the expression of ICAM-1 in human pulmonary type II-like epithelial (A549) cells was evaluated. Conditioned RSV media (cRSV) produced from growth of RSV in A549 cells induced a significant increase in the expression of ICAM-1. Treatment of the cells with noninfectious cRSV prepared by ultraviolet (UV) irradiation (UV-cRSV) or ribavirin treatment resulted in the expression of ICAM-1 to a similar extent as infectious cRSV. These results suggested that RSV induces the synthesis of a soluble mediator(s) that regulates the expression of ICAM-1. Cytokine analysis by immunoassay and polymerase chain reaction showed that RSV induces the synthesis of interleukin (IL)-1 alpha and -beta, and tumor necrosis factor alpha (TNF-alpha). Preincubation of UV-cRSV with soluble IL-1 receptor (sIL-1r) almost completely blocked the enhancement of ICAM-1 expression. Furthermore, simultaneous incubation of infectious purified RSV with sIL-1r resulted in a significant reduction in enhancement of ICAM-1 expression. Preincubation with neutralizing antibodies to IL-1 alpha and -beta, and TNF-alpha showed that the predominant ICAM-1 enhancing soluble mediator in UV-cRSV was IL-1 alpha. These experiments provide direct evidence for an autocrine mechanism of enhanced ICAM-1 expression in RSV-infected epithelial cells that is mediated primarily by IL-1 alpha. Pulmonary epithelial cells may play an important immunoregulatory role in the microenvironment of the lower respiratory tract infected with RSV.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0371, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: Kunimoto
authors.forename: T C
authors.initials: TC
authors.lastname: Sim
authors.forename: R
authors.initials: R
authors.lastname: Garofalo
authors.forename: T
authors.initials: T
authors.lastname: Eliott
authors.forename: S
authors.initials: S
authors.lastname: Baron
authors.forename: O
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: T
authors.initials: T
authors.lastname: Chonmaitree
authors.forename: P L
authors.initials: PL
authors.lastname: Ogra
authors.forename: F
authors.initials: F
authors.lastname: Schmalstieg
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma