Chlamydophila pneumoniae Induces ICAM-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C–Dependent Activation of Nuclear Factor-κB

Abstract

Chlamydophila pneumoniae has an epidemiological link with atherosclerosis and acute cardiovascular events. One mechanism that may explain such a link is the increased expression of intracellular adhesion molecule-1 (ICAM-1) in C pneumoniae –infected endothelial cells. Upregulation of ICAM-1 by C pneumoniae is well recognized and has been extensively studied, but the signaling pathways involved are not yet defined. Because upregulation of ICAM-1 by cytokines and other stimuli has been shown to be mediated by either mitogen-activated protein kinase, protein kinase C (PKC), or nuclear factor-κB (NF-κB) pathways, we examined whether these pathways were involved in the ICAM-1 upregulation induced by C pneumoniae . Our data show a time-dependent phosphorylation of p44/p42 and SAPK/JNK pathways in C pneumoniae –infected cells. However, inhibition of the classic mitogen-activated protein kinase pathway using the PD98059 and U0126 inhibitors and inhibition of SAPK/JNK pathway did not suppress C pneumoniae –induced ICAM-1 expression. C pneumoniae also activates the NF-κB pathway at 30 minutes after infection. Treatment of human aortic endothelial cells (HAECs) with the NF-κB inhibitors BAY117085 and caffeic acid phenethyl ester led to a concentration-dependent inhibition of C pneumoniae –induced ICAM-1 upregulation. Finally, C pneumoniae –infected HAECs show membrane translocation of total PKC 30 minutes after cell infection. Calphostin C, a general PKC inhibitor, blocked both C pneumoniae –induced ICAM-1 expression and C pneumoniae –induced NF-κB translocation. In conclusion, we demonstrated that C pneumoniae –induced ICAM-1 expression in HAECs requires NF-κB and PKC activation and that NF-κB activation is PKC dependent.