Macrophage antioxidant enzymes regulate Chlamydia pneumoniae chronicity: evidence of the effect of redox balance on host-pathogen relationship.
Latency, chronicity and recurrent nature are the features of Chlamydia pneumoniae biology which play a central role in the course and outcome of C. pneumoniae-host interaction. Since redox status is directly an indicator of inflammatory response via molecular signaling mechanisms, we decided to study the regulatory role of macrophage cellular redox balance on the molecular indices of C. pneumoniae chronicity. We examined GSH-GSSG status, the activities of antioxidant enzymes (SOD, GPx and gamma-GCS), along with their protein and gene expression, the MOMP and cHSP-60 protein and gene expression, and the consequence of redox balance on the establishment of productive infection in macrophages. Results showed that C. pneumoniae caused changes in GSH-GSSG levels, antioxidant enzymes activity, mRNA gene and protein expression in macrophages. The relevance of this to the state and status of C. pneumoniae in macrophages was assessed by inhibitor induced attenuation of antioxidant enzymes and there was evidence that, while SOD attenuation did not significantly affect MOMP and cHSP-60 gene and protein expression, gamma-GCS attenuation increased cHSP-60 gene and protein expression. The increase in molecular evidence of chronic forms of C. pneumoniae (cHSP-60) was consistent with decrease in normal forms of C. pneumoniae. These findings reflect the importance of redox balance modulation on the outcome of C. pneumoniae infection in macrophages, a significant process in the pathogenesis of chlamydial diseases.
Azenabor
Anthony A
AA
Department of Health Sciences, University of Wisconsin, Enderis Hall, Room 469, 2400 E. Hartford Avenue, Milwaukee, WI 53211, USA. aazenabo@uwm.edu
Muili
Kamaldeen
K
Akoachere
Jane-Francis
JF
Chaudhry
Abir
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000502:physiology*; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry / Q000201:enzymology* / Q000382:microbiology*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D001425:Bacterial Outer Membrane Proteins; D018834:Chaperonin 60; D017382:Reactive Oxygen Species; C101031:major outer membrane protein, Chlamydia pneumoniae; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014453:Glucuronosyltransferase; D005978:Glutathione; D019803:Glutathione Disulfide