Title |
Chlamydia pneumoniae induces a pro‐inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species
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Published in |
Clinical & Experimental Pharmacology & Physiology, February 2012
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DOI | 10.1111/j.1440-1681.2011.05657.x |
Pubmed ID | |
Authors |
Jennifer Rivera, Anna K Walduck, Richard A Strugnell, Christopher G Sobey, Grant R Drummond |
Abstract |
NADPH oxidases (Nox) are reactive oxygen species (ROS)-generating enzymes that play important physiological roles in host defence and redox signalling. However, Nox activity is upregulated in the vascular wall during atherosclerosis and contributes to plaque formation by promoting oxidative stress and inflammation. The bacterium Chlamydia pneumoniae has been detected in vascular smooth muscle cells (VSMC) of human atheroma. We hypothesized that C. pneumoniae infection of VSMC causes Nox activation, which initially limits infection but ultimately causes oxidative stress, activation of pro-inflammatory pathways and an atherogenic phenotype. Chlamydia pneumoniae infection of mouse cultured VSMC significantly increased ROS production by twofold but did not upregulate mRNA expression of Nox1 or Nox4. Chlamydia pneumoniae did increase Nox2 mRNA levels significantly by threefold, but this did not translate to elevated Nox2 protein expression. The Nox inhibitor gp91ds-tat had no effect on C. pneumoniae-induced ROS production. In contrast, apocynin significantly reduced ROS levels by 75% in C. pneumoniae-infected VSMC, an effect most likely attributable to its direct anti-oxidant action. Although apocynin had no effect on C. pneumoniae-induced expression of inflammatory markers, bacteria recovered from apocynin-treated VSMC displayed a higher degree of infectivity in HEp-2 cells. In conclusion, C. pneumoniae infection increases ROS production in VSMC independently of Nox activity. Although elevated ROS production appears to serve a protective role by limiting the spread of infection, we speculate that this response will be detrimental over the long term by causing oxidative stress and a smouldering inflammatory response by maintaining C. pneumoniae persistence within the cell. |
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Demographic breakdown
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