Cox-2 inhibition abrogates Chlamydia pneumoniae-induced PGE2 and MMP-1 expression.
Peripheral blood monocytes (PBMC) promote vascular inflammation and atherosclerosis. Chlamydia pneumoniae (Cp) infection of PBMC is found in atherosclerotic patients, appears refractory to antibiotics, and may predispose to vascular damage. In Cp-infected human PBMC we analyzed the role of cyclooxygenase-2 (Cox-2) for the proatherosclerotic key mediators prostaglandin E2 (PGE2) and interstitial collagenase (MMP-1). Cp infection resulted in rapid and sustained Cox-2 mRNA and protein stimulation depending on p38 and p44/42 MAPkinases. Subsequent upregulation of PGE synthase and MMP-1 was completely abrogated by the selective Cox-2 inhibitor NS398. Enhanced synthesis of PGE2 and MMP-1 in Cp infected PBMC is mediated through initiation of the p38 and p44/42 MAPK pathways and requires sustained Cox-2 activation. Selective Cox-2 inhibitors, currently under investigation for cardiovascular risk reduction, may represent a novel therapeutic option for patients with endovascular Cp infection as they target the actuated pathological signal transduction cascade in persistently infected PBMC.
Rupp
Jan
J
Institute of Medical Microbiology and Hygiene, University of Luebeck, Germany.
Berger
Mario
M
Reiling
Norbert
N
Gieffers
Jens
J
Lindschau
Carsten
C
Haller
Hermann
H
Dalhoff
Klaus
K
Maass
Matthias
M
D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000378:metabolism* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000382:microbiology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone