Requirement for NF-κB in Transcriptional Activation of Monocyte Chemotactic Protein 1 byChlamydia pneumoniaein Human Endothelial Cells

Open Access
Publisher Website
Google Scholar
Abstract
Infection withChlamydia pneumoniae, a causative agent of acute and chronic respiratory diseases, has recently been implicated as a potential risk factor in atherosclerosis. Atherosclerotic lesions are characterized by monocyte infiltration, which may be regulated by the chemokine monocyte chemotactic protein 1 (MCP-1). We have previously shown thatC. pneumoniaeinfection stimulates MCP-1 production in human endothelial cells, an event which may be specific to this species ofChlamydia, sinceChlamydia trachomatisinfection fails to induce this response. To examine the underlying mechanisms by whichC. pneumoniaeinfection induces MCP-1 production in endothelial cells, the present study investigated the role of transcription factor NF-κB in MCP-1 mRNA expression. Human umbilical vein endothelial cells (HUVEC) were infected with the coronary isolateC. pneumoniaeA-03 or withC. trachomatisL2, and MCP-1 mRNA expression was assessed after different periods of infection by reverse transcription-PCR. Expression of MCP-1 mRNA inC. pneumoniae-infected HUVEC was significantly elevated as early as 1 h postinfection and increased dramatically by 12 and 24 h compared to baseline controls. Nuclear translocation of NF-κB occurred by 30 min of infection, as determined by electrophoretic mobility shift assays and immunofluorescence staining. Treatment ofC. pneumoniae-infected HUVEC with parthenolide, a specific inhibitor of NF-κB activation, suppressed MCP-1 mRNA expression. In contrast, infection withC. trachomatisL2 did not induce MCP-1 mRNA in infected HUVEC and failed to activate NF-κB. Results from this study demonstrate a requirement for NF-κB activation in stimulation of MCP-1 gene expression byC. pneumoniaein human endothelial cells. Furthermore, the data suggest that, within the genusChlamydia, functionally distinct signaling pathways leading to NF-κB activation are utilized byC. pneumoniaein endothelial cells during infection.