Expression of microsomal prostaglandin E synthase-1 in muscle tissue of patients with idiopathic inflammatory myopathies

Background

Microsomal prostaglandin E synthase (mPGES)-1 catalyzes the formation of prostaglandin (PG) E₂ from cyclooxygenase (COX)-derived PGH₂. mPGES-1 is induced by proinflammatory cytokines, such as IL-1β and tumor necrosis factor alpha, and is linked to conditions with high PGE₂ biosynthesis and inflammation. A recent study has demonstrated enhanced COX-1 and COX-2 expressions in affected muscle tissues of patients with polymyositis (PM) and dermatomyositis (DM), suggesting their important role in the pathophysiology of these diseases. However, expression of mPGES-1 in muscle tissue has not been investigated.

Objective

To study the expression of mPGES-1 in muscle tissue of patients with idiopathic inflammatory myopathies.

Methods

Muscle biopsies were obtained from 13 patients with idiopathic inflammatory myopathies (six PM, four DM, one juvenile DM, two inclusion body myositis) and from six healthy subjects. Immunohistochemical analysis was performed using antibodies against mPGES-1.

Results

mPGES-1 staining was detected in all patients with PM, DM and inclusion body myositis. Specifically strong intracellular staining was observed in inflammatory cells in infiltrates, in endothelial cells of capillaries, in scattered mononuclear cells and in fibroblast-like cells. In some patients mPGES-1 staining was localized in smooth muscle cells and endothelial cells of large vessels. In healthy subjects, weak mPGES-1 staining was detected only in scattered fibroblast-like cells, in a few mononuclear cells surrounding large vessels and in some capillaries.

Conclusion

These results demonstrate the upregulation of mPGES-1 in muscle tissue of refractory patients with idiopathic inflammatory myopathies compared with healthy controls, suggesting a role of mPGES-1 in the pathophysiology of these diseases.