Chlamydia pneumoniae enhances cytokine-stimulated human monocyte matrix metalloproteinases through a prostaglandin E2-dependent mechanism

Abstract

Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte-colony stimulating factor. The effect of C. pneumoniae on monocyte MMPs was mediated through the induction of prostaglandin E(2). These findings may have implications for atherosclerotic plaque rupture.

FIG. 1.

C. pneumoniae increases the sensitivity of monocytes to MMP-1 and MMP-9 induction by TNF-α and GM-CSF. Monocytes were incubated with the IFU for 6 h, washed, and cultured in the presence or absence of TNF-α (50 ng/ml) and GM-CSF (50 ng/ml) for an additional 48 h. Supernatants were harvested at 48 h and were assayed for MMP-1 and MMP-9 by Western blotting. Panel A represents a dose response of IFU of live C. pneumoniae, whereas panel B compares IFU of live C. pneumoniae to the equivalent IFU of C. pneumoniae following heating at 90°C for 15 min.

FIG. 2.

Indomethacin and aspirin inhibit C. pneumonia enhancement of MMP-1 and MMP-9. Monocytes were cultured for 6 h with C. pneumoniae (10⁵/ml), washed, and cultured in the presence or absence of TNF-α plus GM-CSF and indomethacin (Indo) (1 μM) or aspirin (Asp) (1 μM) for 48 h. The levels of MMP-1 and -9 in the 48-h supernatants were determined by Western blotting.

FIG. 3.

Induction of PGE₂ by C. pneumoniae. Monocytes were incubated with different concentrations of C. pneumoniae IFU for 6 h, washed, and cultured with or without TNF-α plus GM-CSF for 24 h. The 24-h supernatants were assayed for PGE₂ by ELISA (A) and from cultures treated with 1 μM indomethacin (B). The data are representative of three separate experiments from different donors.