Cox-2 inhibition abrogates Chlamydia pneumoniae-induced PGE2 and MMP-1 expression

Biochemical and Biophysical Research Communications
Jan RuppMatthias Maass

Abstract

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.

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Citations

Aug 5, 2008·Microbial Pathogenesis·Hiroyuki YamaguchiYoshimasa Yamamoto
Jun 6, 2008·International Journal of Antimicrobial Agents·Ying YanPekka Saikku
Oct 27, 2006·Journal of Veterinary Internal Medicine·Anthony T BlikslagerJames K Belknap
May 26, 2005·International Immunopharmacology·Tatsuya SasakawaSeitaro Mutoh
Jul 6, 2014·Pathogens and Disease·Markus LohrPetra Reinhold
Mar 14, 2009·FEMS Immunology and Medical Microbiology·Jan Marco KernMatthias Maass
Feb 18, 2009·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·J M KernM Maass
Jun 15, 2006·Journal of Medical Microbiology·Hideaki IkejimaYoshimasa Yamamoto
Jul 20, 2006·Journal of Medical Microbiology·Liisa TörmäkangasIlari Paakkari

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