ab22402

The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis

J.T. Studýnková¹, S. Kuchen², E. Jeisy², J. Schedel2, F. Charvát³, K. Jarosÿová¹, H. Sprott², M. Matucci-Cerinic⁴, R.E. Gay², B.A. Michel², K. Pavelka¹, J. Vencovský², S. Gay²

¹Institute of Rheumatology, Prague, Czech Republic; ²Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland; ³Radiodiagnostic Department of the Military Hospital, Prague, Czech Republic; ⁴Department of Medicine, Division of Rheumatology, University of Florence, Italy.

ABSTRACT
Objective
To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) - and to find out if any differences between affected and non-affected muscles detected by MRI exist.

Methods
Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA.

Results
Expression of COX-1, COX-2, and 5-LOX mRNA was found in all samples Ð in the muscle cells, inflammatory cells and in vessels. COX-1 mRNA expression predominated in the inflammatory cells and vessels and was higher in affected than in non-affected sites detected by MRI (mean intensity 3.22 ± 0.67 vs. 2.0 ± 0.87; p = 0.0006). The expression of COX-2 mRNA was high mainly in inflammatory cells and/or vessels and was increased in MRI-detected affected tissues (3.5 ± 0.8; 1.9 ± 1.1; p = 0.003), as was the expression of COX-2 mRNA in muscle cells (2.1 ± 1.0 vs. 1.3 ± 1.0; p = 0.021). 5-LOX mRNA was largely expressed in muscle cells from MRI-detected affected sites and the signal intensity was higher in comparison with samples taken from non-affected tissues detected by MRI (3.22 ± 0.7 vs. 1.67 ± 0.7; p = 0.0007).

Conclusion
Expression of COX-1, COX-2 and 5-LOX mRNA was observed for the first time in muscle tissues from IIM patients. This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM.

Key words
Polymyositis, dermatomyositis, COX-1, COX-2, 5-LOX.

The project obtained support from the Internal Grant Agency No. NI/5369-3 and Institutional support No. 00000023728 from the Czech Ministry of Health.
Please address correspondence and reprint requests to: Jirÿ’ Vencovsky«, MD, Institute of Rheumatology, Na Slupi 4, 12850 Praha 2, Czech Republic.
E-mail: venc@revma.cz