Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.
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.
Patel
J A
JA
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0371, USA.
Kunimoto
M
M
Sim
T C
TC
Garofalo
R
R
Eliott
T
T
Baron
S
S
Ruuskanen
O
O
Chonmaitree
T
T
Ogra
P L
PL
Schmalstieg
F
F
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
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma