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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2016 ; 20
(4
): 758-64
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Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial
tight junctions and restricts hyperglycaemia-induced bacterial growth
#MMPMID26837005
J Cell Mol Med
2016[Apr]; 20
(4
): 758-64
PMID26837005
show ga
Lung disease and elevation of blood glucose are associated with increased glucose
concentration in the airway surface liquid (ASL). Raised ASL glucose is
associated with increased susceptibility to infection by respiratory pathogens
including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously
shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus
growth across in vitro airway epithelial cultures. The aim of this study was to
investigate whether metformin has the potential to reduce glucose-induced P.
aeruginosa infections across airway epithelial (Calu-3) cultures by limiting
glucose permeability. We also explored the effect of P. aeruginosa and metformin
on airway epithelial barrier function by investigating changes in tight junction
protein abundance. Apical P. aeruginosa growth increased with basolateral glucose
concentration, reduced transepithelial electrical resistance (TEER) and increased
paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited
the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose
flux. Similar effects on bacterial growth and TEER were observed with the AMP
activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide.
Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction
in the abundance of tight junction proteins, claudin-1 and occludin. Our study
highlights the potential of metformin to reduce hyperglycaemia-induced P.
aeruginosa growth through airway epithelial tight junction modulation, and that
claudin-1 and occludin could be important targets to regulate glucose
permeability across airway epithelia and supress bacterial growth. Further
investigation into the mechanisms regulating metformin and P. aeruginosa action
on airway epithelial tight junctions could yield new therapeutic targets to
prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use
of antibiotics.
|AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism
[MESH]