Document Detail

Klebsiella pneumoniae induces an inflammatory response in an in vitro model of blood-retinal barrier.
MedLine Citation:
PMID:  24478098     Owner:  NLM     Status:  MEDLINE    
Klebsiella pneumoniae has become an important pathogen in recent years. Although most cases of K. pneumoniae endogenous endophthalmitis occur via hematogenous spread, it is not yet clear which microbial and host factors are responsible for the ability of K. pneumoniae to cross the blood-retinal barrier (BRB). In the present study, we show that in an in vitro model of BRB based on coculturing primary bovine retinal endothelial cells (BREC) and primary bovine retinal pericytes (BRPC), K. pneumoniae infection determines changes of transendothelial electrical resistance (TEER) and permeability to sodium fluorescein. In the coculture model, bacteria are able to stimulate the enzyme activities of endothelial cytosolic and Ca(2+)-independent phospholipase A2s (cPLA2 and iPLA2). These results were confirmed by the incremental expression of cPLA2, iPLA2, cyclo-oxygenase-1 (COX1), and COX2 in BREC, as well as by cPLA2 phosphorylation. In supernatants of K. pneumoniae-stimulated cocultures, increases in prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-8, and vascular endothelial growth factor (VEGF) production were found. Incubation with K. pneumoniae in the presence of arachidonoyl trifluoromethyl ketone (AACOCF3) or bromoenol lactone (BEL) caused decreased PGE2 and VEGF release. Scanning electron microscopy and transmission electron microscopy images of BREC and BRPC showed adhesion of K. pneumoniae to the cells, but no invasion occurred. K. pneumoniae infection also produced reductions in pericyte numbers; transfection of BREC cocultured with BRPC and of human retinal endothelial cells (HREC) cocultured with human retinal pericytes (HRPC) with small interfering RNAs (siRNAs) targeted to cPLA2 and iPLA2 restored the pericyte numbers and the TEER and permeability values. Our results show the proinflammatory effect of K. pneumoniae on BREC, suggest a possible mechanism by which BREC and BRPC react to the K. pneumoniae infection, and may provide physicians and patients with new ways of fighting blinding diseases.
C Motta; M Salmeri; C D Anfuso; A Amodeo; M Scalia; M A Toscano; G Giurdanella; M Alberghina; G Lupo
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-12-09
Journal Detail:
Title:  Infection and immunity     Volume:  82     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-01-30     Completed Date:  2014-04-08     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  851-63     Citation Subset:  IM    
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MeSH Terms
Blood-Retinal Barrier / microbiology*,  pathology*
Cells, Cultured
Coculture Techniques
Endothelial Cells / microbiology*,  physiology
Gene Expression Profiling
Inflammation / microbiology*,  physiopathology*
Inflammation Mediators / metabolism
Klebsiella pneumoniae / immunology*,  pathogenicity
Pericytes / microbiology*,  physiology
Reg. No./Substance:
0/Inflammation Mediators

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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