NF-kappaB and inhibitor of apoptosis proteins are required for apoptosis resistance of epithelial cells persistently infected with Chlamydophila pneumoniae.
Infection with Chlamydophila pneumoniae (Cpn) renders host cells resistant to apoptosis induced by a variety of stimuli. While modulation of apoptosis has been extensively studied in cells acutely infected with Cpn, very little is known on how persistent chlamydial infection influences host cell survival. Here we show that epithelial cells persistently infected with Cpn resist apoptosis induced with TNFalpha or staurosporine. Cpn induced the activation of nuclear factor kappa B (NF-kappaB) and inhibition of NF-kappaB with a chemical inhibitor or by silencing expression of the p65 subunit sensitized infected cells for apoptosis induction by staurosporine or TNFalpha. Persistent infection resulted in the upregulation of the NF-kappaB regulated inhibitor of apoptosis protein 2 (cIAP-2) but not inhibitor of apoptosis protein 1 (cIAP-1). Interestingly, silencing of either cIAP-1 or cIAP-2 sensitized infected cells, suggesting that IAPs play an important role in the apoptosis resistance of persistently infected cells.
Paland
Nicole
N
Max Planck Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany.
Rajalingam
Krishnaraj
K
Machuy
Nikolaus
N
Szczepek
Agnes
A
Wehrl
Wolfgang
W
Rudel
Thomas
T
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D004847:Epithelial Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D053181:Caspase 8; D019311:Staurosporine