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 pneumonia, has been detected in vascular smooth muscle cells (VSMCs) of human atheroma. We hypothesised that C. pneumoniae infection of VSMCs causes Nox activation, which initially limits infection, but ultimately causes oxidative stress, activation of pro-inflammatory pathways and an atherogenic phenotype. C. pneumoniae infection of mouse cultured VSMCs increased ROS production but did not upregulate mRNA expression of Nox1 or Nox4. C. pneumoniae did increase Nox2 mRNA levels but this did not translate to elevated Nox2 protein expression. The Nox inhibitor, gp91ds-tat, had no effect on C. pneumoniae-induced ROS production. By contrast, apocynin reduced ROS levels in C. pneumoniae-infected VSMCs, an effect most likely attributable to it direct antioxidant actions. Although apocynin had no effect on C. pneumoniae-induced expression of inflammatory markers, bacteria recovered from apocynin-treated VSMCs displayed a higher degree of infectivity in HEp-2 cells. In conclusion, C. pneumoniae infection increases ROS production in VSMCs independently of Nox activity. While 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. (c) 2011 The Authors Clinical and Experimental Pharmacology and Physiology (c) 2011 Blackwell Publishing Asia Pty Ltd.
|Pages (from-to)||218 - 226|
|Number of pages||9|
|Journal||Clinical and Experimental Pharmacology and Physiology|
|Publication status||Published - 2012|
Rivera, J., Walduck, A. K., Strugnell, R. A., Sobey, C. G., & Drummond, G. R. (2012). Chlamydia pneumoniae induces a pro-inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species. Clinical and Experimental Pharmacology and Physiology, 39(3), 218 - 226. https://doi.org/10.1111/j.1440-1681.2011.05657.x