Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0032285 (
pneumonia
)
54,520
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pseudomonas aeruginosa is a major cause of
pneumonia
in patients with cystic fibrosis and other immuncompromising conditions. Here we showed that P. aeruginosa invades type I pneumocytes via a lipid raft-mediated mechanism. P. aeruginosa invasion of rat primary type I-like pneumocytes as well as a murine lung epithelial cell line 12 (MLE-12) is inhibited by drugs that remove membrane cholesterol and disrupt lipid rafts. Confocal microscopy demonstrated co-localization of intracellular P. aeruginosa with lipid raft components including caveolin-1 and -2. We generated caveolin-1 and -2 knockdowns in MLE-12 cells by using RNA interference techniques. Decreased expression of
caveolin-2
significantly impaired the ability of P. aeruginosa to invade MLE-12 cells. In addition, the lipid raft-dependent tyrosine phosphorylation of
caveolin-2
appeared to be a critical regulator of P. aeruginosa invasion.
...
PMID:Pseudomonas invasion of type I pneumocytes is dependent on the expression and phosphorylation of caveolin-2. 1554 64
Pseudomonas aeruginosa has the capacity to invade lung epithelial cells by co-opting the intrinsic endocytic properties of lipid rafts, which are rich in cholesterol, sphingolipids, and proteins, such as caveolin-1 and -2. We compared intratracheal Pseudomonas infection in wild type and caveolin-deficient mice to investigate the role of caveolin proteins in the pathogenesis of Pseudomonas
pneumonia
. Unlike wild type mice, which succumb to
pneumonia
, caveolin-deficient mice are resistant to Pseudomonas. We observed that Pseudomonas invasion of lung epithelial cells is dependent on
caveolin-2
but not caveolin-1. Phosphorylation of
caveolin-2
by Src family kinases is an essential event for Pseudomonas invasion. Our studies also reveal the existence of a distinct signaling mechanism in lung epithelial cells mediated by COOH-terminal Src kinase (Csk) that negatively regulates Pseudomonas invasion. Csk migrates to lipid raft domains, where it decreases phosphorylation of
caveolin-2
by inactivating c-Src. Whereas Pseudomonas co-opts the endocytic properties of
caveolin-2
for invasion, there also exists in these cells an intrinsic Csk-dependent cellular defense mechanism aimed at impairing this activity. The success of Pseudomonas in co-opting lipid raft-mediated endocytosis to invade lung epithelial cells may depend on the relative strengths of these counteracting signaling activities.
...
PMID:Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa. 1921 60
