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Differential Expression of Leukotriene B4 Receptor Subtypes (BLT1 and BLT2) in Human Synovial Tissues and Synovial Fluid Leukocytes of Patients with Rheumatoid Arthritis
ATSUSHI HASHIMOTO, HIRAHITO ENDO, IZUMI HAYASHI, YOUSUKE MURAKAMI, HIDERO KITASATO, SHIZUKA KONO, TOSHIMICHI MATSUI, SUMIAKI TANAKA, AKITO NISHIMURA, KEN URABE, MORITOSHI ITOMAN, and HIROBUMI KONDO
ABSTRACT.
Methods. BLT1 and BLT2 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization in synovial tissues from 40 patients with RA and 10 patients with OA. Results. BLT2 (the low-affinity receptor for LTB4) showed stronger expression than BLT1 (the high-affinity receptor) in actively inflamed synovial tissue from patients with RA. Synovial macrophages, fibroblast-like cells, and lymphocytes expressed BLT2 mRNA in RA synovial tissues showing active inflammation. BLT2 mRNA was strongly expressed in the synovial lining cells, which also expressed 5-lipoxygenase, an enzyme that synthesizes LTB4. BLT1 and BLT2 mRNA expression in synovial tissues was stronger in RA than in OA by real-time quantitative PCR. In contrast, leukocytes infiltrating synovial fluid predominantly expressed BLT1 mRNA in patients with RA. It was recently reported that these 2 receptors for LTB4 have quite different pharmacological effects and a different tissue distribution. Conclusion. BLT2 is the main receptor mediating the effects of LTB4 in the synovial tissues of patients with RA; this suggests the possibility of developing a new therapy to block LTB4 in inflammatory arthritis. (J Rheumatol 2003;30:1712-8) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Division of Rheumatology, Departments of Internal Medicine, Pharmacology, Microbiology, and Orthopedics, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa, Japan. Supported in part by grants-in-aid from the Japan Ministry of Education, Science, and Sports, and by a Parents' Association Grant, Kitasato University School of Medicine. A. Hashimoto, MD; H. Endo, MD, PhD, Assistant Professor, Division of Rheumatology, Department of Internal Medicine; I. Hayashi, PhD, Associate Professor, Department of Pharmacology; Y. Murakami, MS; H. Kitasato, PhD, Assistant Professor, Department of Microbiology; S. Kono, MD; T. Matsui, MD, PhD; S. Tanaka, MD, PhD, Division of Rheumatology, Department of Internal Medicine; A. Nishimura, MD, PhD, Assistant Professor; K. Urabe, MD, PhD, Assistant Professor; M. Itoman, MD, PhD, Professor, Department of Orthopedics; H. Kondo, MD, PhD, Professor, Division of Rheumatology, Department of Internal Medicine. Address reprint requests to Dr. H. Endo, Department of Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. E-mail hiraendo@med.kitasato-u.ac.jp Submitted August 22, 2002; revision accepted January 8, 2003. |