Methods: Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumonia infection. Dexamethasone was used in each experiment to assess the responsiveness to the corticosteroid. The values of secreted MMP-9 and TIMP-1 were measured by ELISA. To evaluate the underlying mechanism, the expression of human glucocorticoid receptor (GR)-β, known as an endogenous antidote for GR, was observed in PBMCs with or without C. pneumoniae infection using immunohistochemistry.
Results: The secretion of MMP-9 and TIMP-1 was remarkably suppressed by corticosteroid treatment in PBMCs without C. pneumoniae infection. In C. pneumoniea-infected PBMCs, the suppressed secretion of MMP-9 by the corticosteroid was significantly inhibited, while the level of TIMP-1 secretion did not change compared with those levels in untreated PBMCs. Therefore, the molar ratio of secreted MMP-9/TIMP-1 was decreased by C. pneumonia infection and was more exaggerated under corticosteroid treatment. The expression of GR-β was significantly increased in C. pneumoniae-infected PBMCs.
Conclusion: C. pneumoniae infection in inflammatory cells may induce altered secretion of tissue enzymes associated with airway remodeling through a decreased responsiveness to corticosteroids and may be linked to the pathogenesis of severe asthma.
Key words: Asthma, Chlamydophila pneumoniae, Peripheral blood mononuclear cells, MMP-9, TIMP-1, glucocorticoid receptor (GR) - β