Interferon-beta induction by Chlamydia pneumoniae in human smooth muscle cells.

Clinical studies have suggested a causal or contributory role of Chlamydia pneumoniae infection in asthma and atherosclerosis. The activation of synthetic functions of smooth muscle cells (SMC) including the production of cytokines and growth factors plays a major role in the formation of fibrous atherosclerotic plaques as well as in structural remodelling of the airway wall in chronic asthma. In this study we demonstrated that C. pneumoniae induced the production of low levels of interferon (IFN)-beta in bronchial and vascular SMC when infected cells were treated with tumour necrosis factor-alpha (TNF-alpha). IFN-beta production was analysed by reverse transcription-PCR and enzyme-linked immunosorbent assay. The upregulation of IFN-beta was paralleled by an increase in mRNA levels of interferon regulatory factor-1 and interferon-stimulated gene factor 3gamma, two transcription factors activating the expression of the IFN-beta gene. In addition, C. pneumoniae infection enhanced the mRNA level of indoleamine 2,3-dioxygenase, an IFN-inducible factor mediating the restriction of intracellular chlamydial growth, in TNF-alpha-stimulated SMC. C. pneumoniae-induced IFN-beta production by SMC may modulate inflammation and tissue remodelling during respiratory and vascular infection.

Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae.

Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.