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.
Institute of Clinical Chemistry and Pathobiochemistry, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 München, Germany.
Bernadette
B
Donath
Claudia
C
Fischer
Sharon
S
Page
Sigrid
S
Prebeck
Nikolaus
N
Jilg
Marion
M
Weber
Clarissa
C
da Costa
Dieter
D
Neumeier
Thomas
T
Miethke
Korbinian
K
Brand
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