Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages
Amir Kol, … , Andrew H. Lichtman, Peter Libby
Amir Kol, … , Andrew H. Lichtman, Peter Libby
Published February 15, 1999
Citation Information: J Clin Invest. 1999;103(4):571-577. https://doi.org/10.1172/JCI5310.
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Article

Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages

Abstract

Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-κB (NF-κB), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-κB complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability of E. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.

Authors

Amir Kol, Todd Bourcier, Andrew H. Lichtman, Peter Libby

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Human HSP 60 induces NF-κB activation: identification of p65 and p50 Rel...
Human HSP 60 induces NF-κB activation: identification of p65 and p50 Rel proteins as components of DNA-binding complexes. Endothelial cells were incubated with medium only (unstimulated control), or with human HSP 60 (2 μg/ml) for 2 h. Rel proteins were identified by performing electromobility shift assay on nuclear extracts, with an oligonucleotide containing the NF-κB–binding site of the IL-6 promoter, in the presence of the indicated Rel antisera or with nonimmune rabbit IgG. NF-κB and supershifted complexes are indicated on the left: p65 (Rel A) and p50 were identified as components of human HSP–induced binding complexes, while antibodies to cRel, RelB, or nonimmune rabbit IgG did not shift any binding complex. Probeonly indicates electromobility shift assay performed without nuclear extract.