Chlamydia pneumoniae activates IKK/IκB-mediated signaling, which is inhibited by 4-HNE and following primary exposure

Chlamydia pneumoniae may be involved in atherosclerosis by inducing inflammation as well as LDL oxidation. The transcription factor NF-kappaB is found in an active state in atherosclerotic lesions. This study examined the effect of-C pneumoniae exposure on the NF-kappaB system in human monocytic lineage cells. Short exposure to C pneumoniae as well as chlamydial heat shock protein 60 activated NF-kappaB, accompanied by increased cytokine production. Incubation with C pneumoniae induced depletion Of IkappaB-alpha and later IkappaB-epsilon which was preceded by IkappaB kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C pneumoniae induced NF-kappaB activation by preventing IkappaB phosphorylation/proteolysis. During long-term incubation with C pneumoniae IkappaB-alpha returned to baseline, whereas the levels of IkappaB-epsilon and p65 were upregulated. Interestingly, long-term preincubation with C pneumoniae selectively prevented restimulation by this microorganism, which appears to be at least partly facilitated by inhibition of IkappaB proteolysis. C pneumoniae-induced NF-kappaB activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease. (C) 2002 Published by Elsevier Science Ireland Ltd.