Chlamydia pneumoniae activates IKK/I kappa B-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-kappa B is found in an active state in atherosclerotic lesions. This study examined the effect of C. pneumoniae exposure on the NF-kappa B system in human monocytic lineage cells. Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60 activated NF-kappa B, accompanied by increased cytokine production. Incubation with C. pneumoniae-induced depletion of I kappa B-alpha and later I kappa B-epsilon which was preceded by I kappa B kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C. pneumoniae induced NF-kappa B activation by preventing I kappa B phosphorylation/proteolysis. During long-term incubation with C. pneumoniae I kappa B-alpha returned to baseline, whereas the levels of I kappa B-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 I kappa B proteolysis. C. pneumoniae-induced NF-kappa B activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease.
Donath
Bernadette
B
Institute of Clinical Chemistry and Pathobiochemistry, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 München, Germany.
Fischer
Claudia
C
Page
Sharon
S
Prebeck
Sigrid
S
Jilg
Nikolaus
N
Weber
Marion
M
da Costa
Clarissa
C
Neumeier
Dieter
D
Miethke
Thomas
T
Brand
Korbinian
K
D000447:Aldehydes / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000502:physiology*; D003470:Culture Media; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D009000:Monocytes; D016328:NF-kappa B / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D000447:Aldehydes; D003470:Culture Media; D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C027576:4-hydroxy-2-nonenal