Chlamydophila pneumoniae inhibits corticosteroid-induced suppression of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells

Abstract

Chlamydophila pneumoniae infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodelling. We investigated whether C. pneumoniae infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumoniae. Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in C. pneumoniae-infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor b, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in C. pneumoniae-infected PBMCs. We conclude that C. pneumoniae infection may promote airway remodelling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.

Leukocyte-derived matrix metalloproteinase-9 in patients with coronary artery disease : Associations with psychological stress and glucocorticoid sensitivity

“…After 19 h culture, the mRNA expression and protein secretion of MMP-9 was efficiently suppressed by dexamethasone in both patients and controls, as shown in Table 8. The findings are in agreement with several previous studies reporting dexamethasone-induced inhibition of MMP-9 in a variety of cell types, including human PBMCs (82,84,(186)(187)(188). Also, in clinical settings, glucocorticoid treatment has been shown to induce a rapid decrease in MMP-9, both in circulation and in cerebrospinal fluid (189,190).…”

“…In contrast to MMP-9, the dexamethasone-induced suppression of TIMPs has been less studied and results are contradictory. Prior studies have reported that dexamethasone suppressed the secretion of TIMP-1 in PBMCs and fibroblasts (83,187), while another study showed increased release in alveolar macrophages (84). We found that mRNA expression as well as secretion of TIMP-1 and TIMP-2 was suppressed by dexamethasone and moreover, data indicated an increased sensitivity to GC in post-ACS patients.…”

“…Dexamethasone, a synthetic GC, has been shown in vitro to strongly decrease the secretion of MMP-9 and TIMP-1 in PBMCs (81). The GC-mediated suppression of MMP-9 is also prominent in other cell types (82)(83)(84).…”

Chlamydia pneumoniae Influence on Cytokine Production in Steroid-Resistant and Steroid-Sensitive Asthmatics

“…However, C. pneumoniae infection increased TIMP-1 secretion, leading to a decreased MMP-9/TIMP-1 ratio. Moreover, dexamethasone treatment resulted in a further reduction of this ratio [22]. In this study, we measured the serum MMP-9 levels to define differences related to the C. pneumoniae-specific IgG serostatus and steroid responsiveness.…”

Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolides

“…This shift in response significantly impedes the ability of the host to eradicate intracellular pathogens like CP and may lead to the release of cHSP60 which exacerbates the inflammatory process [11]. There is also evidence that CP infection may promote airway remodeling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids [65]. See Fig.…”