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-κB is found in an active state in atherosclerotic lesions. This study examined the effect of C. pneumoniae exposure on the NF-κB system in human monocytic lineage cells. Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60 activated NF-κB, accompanied by increased cytokine production. Incubation with C. pneumoniae-induced depletion of IκB-α and later IκB- which was preceded by IκB kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C. pneumoniae induced NF-κB activation by preventing IκB phosphorylation/proteolysis. During long-term incubation with C. pneumoniae IκB-α returned to baseline, whereas the levels of IκB- 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 IκB proteolysis. C. pneumoniae-induced NF-κB activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease.