1655 Chlamydophila pneumoniae-infected human peripheral mononuclear cells resist corticosteroid- induced suppression of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion

Monday, 6 December 2010
  Background: It has been suggested that Chlamydophila pneumoniae infection contributes to the development of severe asthma. The major characteristics of severe asthma include a reduced response to corticosteroid treatment and progressive airway remodeling in which an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) is believed to have an important role. We hypothesized that C. pneumoniae infection affects the secretion of MMP-9 and TIMP-1 and induces altered responsiveness to corticosteroids in inflammatory cells.

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