Antiinflammatory mediator lipoxin A4 and its receptor in synovitis of patients with rheumatoid arthritis.
OBJECTIVE
To evaluate the role of an antiinflammatory lipid mediator, lipoxin A4 (LXA4), in inflammatory arthritis, we measured the level of LXA4 in synovial fluid and lipoxin A4 receptor (ALX) expression in synovial tissues obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).


METHODS
Levels of LXA4 and its analog (15-epi-LXA4) in synovial fluid from 30 patients with RA and 15 patients with OA were measured by a specific ELISA. Reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and in situ hybridization were performed to detect mRNA for ALX and 15-LOX, and LXA4 synthetase, in synovial tissues from 20 patients with RA and 10 patients with OA. RESULTS Both LXA4 and 15-epi-LXA4 showed significantly higher levels in RA synovial fluid (10.34 +/- 14.12 ng/ml for LXA4) than OA synovial fluid (0.66 +/- 0.77 ng/ml for LXA4). Logarithmic concentration of LXA4 was significantly correlated with that of leukotriene B4 and prostaglandin E2 in RA and OA synovial fluids. Expressions of ALX and 15-LOX mRNA were stronger in RA synovium than OA synovium. Expression of mRNA for interleukin 13 (IL-13), which induces 15-LOX, was significantly stronger in RA synovium than OA synovium.


CONCLUSIONS
ALX is an important target of LXA4 in synovial tissues of patients with RA. 15-LOX induced by IL-13 might regulate the production of LXA4 to have an antiinflammatory effect against proinflammatory lipid mediators in inflamed joints. These findings could lead to the development of new therapy for inflammatory arthritis such as RA.
Hashimoto
Atsushi
A
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan. hashi@med.kitasato-u.ac.jp
Hayashi
Izumi
I
Murakami
Yousuke
Y
Sato
Yoshinori
Y
Kitasato
Hidero
H
Matsushita
Reiko
R
Iizuka
Nobuko
N
Urabe
Ken
K
Itoman
Moritoshi
M
Hirohata
Shunsei
S
Endo
Hirahito
H
D000328:Adult; D000368:Aged; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000235:genetics; D044045:Lipoxins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D013585:Synovitis / Q000150:complications / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; C105101:FPR2 protein, human; C508598:IL4 protein, human; D044045:Lipoxins; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4; D015847:Interleukin-4; C084486:lipoxin A4 synthase; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase