Nejvíce citovaný článek - PubMed ID 17466590
Lower respiratory tract infection due to Pseudomonas aeruginosa has become increasingly challenging, resulting in a worse morbidity and mortality. Airway remodeling is a common phenomenon in this process, to which epithelial-mesenchymal transition (EMT) may contribute as an important promoter. Previous studies showed that epithelium-specific integrin αvβ6-mediated EMT was involved in pulmonary fibrosis via transforming growth factor-β1 (TGF-β1) signaling, but whether integrin αvβ6 plays a role in the P. aeruginosa-associated airway remodeling remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) from P. aeruginosa in the presence or the absence of integrin αvβ6-blocking antibodies. Morphologic changes were observed by an inverted microscopy. The EMT markers were detected using Western blotting and immunofluorescence. The activation of TGF-β1-Smad2/3 signaling pathway was assessed. Furthermore, matrix metalloproteinase (MMP)-2 and -9 in the medium were measured using ELISA. P. aeruginosa's LPS decreased the expression of the epithelial marker E-cadherin and promoted the mesenchymal markers, vimentin and α-smooth muscle actin in BEAS-2B cells. The expression of integrin αvβ6 was significantly increased during EMT process. Blocking integrin αvβ6 could attenuate P. aeruginosa's LPS-induced EMT markers' expression via TGF-β1-Smad2/3 signaling pathway. Furthermore, blocking integrin αvβ6 could prevent morphologic changes and oversecretion of MMP-2 and -9. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of P. aeruginosa via TGF-β1-Smad2/3 signaling pathway and might be a promising therapeutic target for P. aeruginosa-associated airway remodeling.
- MeSH
- antigeny nádorové genetika metabolismus MeSH
- epitelo-mezenchymální tranzice * MeSH
- epitelové buňky cytologie účinky léků metabolismus MeSH
- integriny genetika metabolismus MeSH
- lidé MeSH
- lipopolysacharidy metabolismus MeSH
- matrixové metaloproteinasy genetika metabolismus MeSH
- protein Smad2 genetika metabolismus MeSH
- protein Smad3 genetika metabolismus MeSH
- pseudomonádové infekce genetika metabolismus mikrobiologie patofyziologie MeSH
- Pseudomonas aeruginosa metabolismus MeSH
- signální transdukce MeSH
- transformující růstový faktor beta1 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny nádorové MeSH
- integrin alphavbeta6 MeSH Prohlížeč
- integriny MeSH
- lipopolysacharidy MeSH
- matrixové metaloproteinasy MeSH
- protein Smad2 MeSH
- protein Smad3 MeSH
- SMAD2 protein, human MeSH Prohlížeč
- SMAD3 protein, human MeSH Prohlížeč
- transformující růstový faktor beta1 MeSH
The aim of this study was to analyse genotypes, antimicrobial susceptibility patterns and serotypes in Pseudomonas aeruginosa clinical strains, including the clonal dissemination of particular strains throughout various intensive care units in one medical centre. Using random amplified polymorphic DNA (RAPD-PCR) and P. aeruginosa antisera, 22 different genotypes and 8 serotypes were defined among 103 isolates from 48 patients. No direct association between P. aeruginosa strain genotypes and serotypes was observed. RAPD typing in strains with the same serotype revealed different genotypes and, on the contrary, most strains with a different serotype displayed the same amplification pattern. The resulting banding patterns showed a high degree of genetic heterogeneity among all isolates from the patients examined, suggesting a non-clonal relationship between isolates from these patients. A higher degree of antibiotic resistance and stronger biofilm production in common genotypes compared to rare ones and genetic homogeneity of the most resistant strains indicated the role of antibiotic pressure in acquiring resistant and more virulent strains in our hospital. In conclusion, genetic characterisation of P. aeruginosa strains using RAPD method was shown to be more accurate in epidemiological analyses than phenotyping.
- Klíčová slova
- Antibiotic Susceptibility, Antimicrobial Susceptibility Pattern, Common Genotype, Meropenem, Unique Genotype,
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence MeSH
- biofilmy * MeSH
- dospělí MeSH
- genotyp MeSH
- jednotky intenzivní péče statistika a číselné údaje MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mladý dospělý MeSH
- pseudomonádové infekce mikrobiologie MeSH
- Pseudomonas aeruginosa účinky léků genetika izolace a purifikace fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- technika náhodné amplifikace polymorfní DNA MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH