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Innate Immunity
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Article

Up-regulation of integrin expression in lung adenocarcinoma cells caused by bacterial infection: in vitro study

Sean Gravelle, Rebecca Barnes, Nicole Hawdon, Lee Shewchuk, Joseph Eibl, Joseph S Lam, and Marina Ulanova*

Ontario School of Medicine West Campus, Lakehead University

* To whom correspondence should be addressed. E-mail: marina.ulanova{at}normed.ca.


  Abstract

Integrins are a large family of adhesion receptors that are known to be key signaling molecules in both physiological and pathological processes. Previous studies have demonstrated that the expression of integrin receptors in the pulmonary epithelium can change under various pathological conditions, such as injury, inflammation, or malignant transformation. We hypothesize that integrin expression can be altered by stimulation of lung epithelial cells with an opportunistic bacterial pathogen Pseudomonas aeruginosa. Using the A549 adenocarcinoma cell line that expressed a low level of several integrin subunits we have demonstrated that P. aeruginosa infection in vitro caused a rapid up-regulation of {alpha}5, {alpha}v, {beta}1, and {beta}4 integrins at both the mRNA and protein level. Neither heat-killed P. aeruginosa strain PAK nor its live isogenic mutants lacking pili or lipopolysaccharide (LPS) core oligosaccharide showed any effect on integrin expression in A549 cells as compared to the use of the wild-type PAK strain. These results establish that up-regulation of integrin expression is dependent on the internalization of live bacteria possessing intact pili and LPS. Gene silencing of integrin-linked kinase in A549 cells caused a significant decrease in the release of pro-inflammatory cytokines in response to P. aeruginosa stimulation. Although further studies are warranted towards understanding the precise role of integrin receptors in prominent inflammation caused by P. aeruginosa, our findings suggest a possibility of using specific integrin inhibitors for therapy of pulmonary inflammatory conditions caused by pathogenic micro-organisms.

First published on August 26, 2009
Innate Immunity 2009, doi:10.1177/1753425909106170
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