Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis.
To evaluate the role of leukotriene B4 (LTB4) receptors in inflammatory arthritis, we investigated the expression of BLT1 and BLT2 mRNA in synovial tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 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.
Hashimoto
Atsushi
A
Division of Rheumatology, Department of Internal Medicine, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa, Japan.
Endo
Hirahito
H
Hayashi
Izumi
I
Murakami
Yousuke
Y
Kitasato
Hidero
H
Kono
Shizuka
S
Matsui
Toshimichi
T
Tanaka
Sumiaki
S
Nishimura
Akito
A
Urabe
Ken
K
Itoman
Moritoshi
M
Kondo
Hirobumi
H
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D018102:Receptors, Leukotriene B4 / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology
C485878:LTB4R2 protein, human; D012333:RNA, Messenger; D018102:Receptors, Leukotriene B4