Antiinflammatory mediator lipoxin A4 and its receptor in synovitis of patients with rheumatoid arthritis

• Published in: Journal of rheumatology Vol. 34; no. 11; pp. 2144 - 2153
• Main Authors: HASHIMOTO, Atsushi, HAYASHI, Izumi, ENDO, Hirahito, MURAKAMI, Yousuke, SATO, Yoshinori, KITASATO, Hidero, MATSUSHITA, Reiko, IIZUKA, Nobuko, URABE, Ken, ITOMAN, Moritoshi, HIROHATA, Shunsei
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-11-2007; Journal of Rheumatology Publishing
• Subjects: Adult; Aged; Arachidonate 12-Lipoxygenase - genetics; Arachidonate 15-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - genetics; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Base Sequence; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Diseases of the osteoarticular system; DNA Primers - genetics; Female; Humans; In Situ Hybridization; Inflammatory joint diseases; Interleukin-4 - genetics; Lipoxins - metabolism; Male; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Osteoarthritis - complications; Osteoarthritis - genetics; Osteoarthritis - metabolism; Pharmacology. Drug treatments; Receptors, Formyl Peptide - genetics; Receptors, Formyl Peptide - metabolism; Receptors, Lipoxin - genetics; Receptors, Lipoxin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Synovial Fluid - metabolism; Synovitis - complications; Synovitis - genetics; Synovitis - metabolism; Human; Immunopathology; Synovitis; Diseases of the osteoarticular system; Antiinflammatory agent; Autoimmune disease; Inflammatory joint disease; Arthritis; Inflammation; Interleukin 13; Joint; Polymerase chain reaction; Chronic; Treatment; Synovial membrane; Rheumatoid arthritis; LIPOXIN; Arthropathy; Degenerative disease; Molecular biology; LIPOXIN A4; Osteoarthritis; Reverse transcription polymerase chain reaction; ELISA assay
• ISSN: 0315-162X; 1499-2752

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. CONCLUSION:
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.