Up-regulation of integrin expression in lung adenocarcinoma cells caused by bacterial infection: in vitro study.
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 alpha5, alphav, beta1, and beta4 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 proinflammatory 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.
Gravelle
Sean
S
Medical Sciences Division, Northern Ontario School of Medicine West Campus, Ontario, Canada, Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
Barnes
Rebecca
R
Hawdon
Nicole
N
Shewchuk
Lee
L
Eibl
Joseph
J
Lam
Joseph S
JS
Ulanova
Marina
M
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D034741:RNA, Small Interfering; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation
D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D016023:Integrins; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases