Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.

J. A. Patel, M. Kunimoto, T. C. Sim, R. Garofalo, T. Eliott, S. Baron, O. Ruuskanen, T. Chonmaitree, P. L. Ogra, F. Schmalstieg

Research output: Contribution to journalArticle

112 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)602-609
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume13
Issue number5
DOIs
StatePublished - Nov 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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