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Effects of immunosuppressive treatment on microsomal PGE synthase 1 and cyclooxygenases expression in muscle tissue of patients with polymyositis or dermatomyositis.
  1. Marina Korotkova (marina.korotkova{at}ki.se)
  1. Rheumatology Unit, Department of medicine, Karolinska Institutet, Sweden
    1. Sevim Barbasso Helmers (sevim.barbasso{at}ki.se)
    1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
      1. Ingela Loell (ingela.loell{at}ki.se)
      1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
        1. Helene Alexanderson (helene.alexanderson{at}karolinska.se)
        1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
          1. Cecilia Grundtman (cecilia.grundtman{at}ki.se)
          1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
            1. Christina Dorph (christina.dorph{at}cmm.ki.se)
            1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
              1. Ingrid E Lundberg (ingrid.lundberg{at}ki.se)
              1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
                1. Per-Johan Jakobsson (per-johan.jakobsson{at}ki.se)
                1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden

                  Abstract

                  Objectives: To investigate the expression of microsomal PGE synthase 1 (mPGES-1) and cyclooxygenase (COX) in muscle biopsies from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment.

                  Methods: mPGES-1 and COX expression was evaluated by immunohistochemistry in muscle tissue from healthy individuals and from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment. The number of inflammatory cell infiltrates, T lymphocytes and macrophages was estimated before and after treatment. To localize the mPGES-1 expression double immunofluorescence was performed with antibodies against mPGES-1, CD3, CD68, CD163 and a fibroblast marker. Functional index was used to assess muscle function.

                  Results: In myositis patients, mPGES-1, COX-2 and COX-1 expression was significantly higher compared to healthy individuals and associated with inflammatory cells. Double immunofluorescence demonstrated a predominant expression of mPGES-1 in macrophages. Conventional immunosuppressive treatment resulted in improved but still lower muscle function than normal. A decreased number of CD68-positive macrophages and reduced COX-2 expression in muscle tissue was also seen. In contrast, following the same treatment no significant changes were observed in muscle tissue regarding number of infiltrates, T lymphocytes, CD163-positive macrophages or mPGES-1 protein levels.

                  Conclusions: Increased expression of mPGES-1, COX-1 and COX-2 at protein level was observed in muscle tissue from myositis patients compared to healthy individuals. Conventional immunosuppressive treatment led to a significant down-regulation of COX-2 in myositis muscle tissue. However, the expression of mPGES-1 and COX-1 remained unchanged indicating a role of these enzymes in the chronicity of these diseases.

                  • dermatomyositis
                  • glucocorticoids
                  • inflammation
                  • polymyositis
                  • prostaglandins

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