Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase-2/prostaglandin E(2) production via CD44 in interleukin-1-stimulated subacromial synovial fibroblasts from patients with rotator cuff disease.
A growing body of evidence supports use of intraarticular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti-inflammatory action has not been clarified. We examined the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha and COX-2/PGE(2) production in IL-1-stimulated subacromial-synovium fibroblasts (SSF) derived from patients with rotator cuff disease. Various concentrations of HA were added to monolayer SSF cultures in the presence of IL-1beta. Gene expression levels were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Intracellular production of COX-2 was identified by Western blotting. PGE(2) concentrations in the culture media were measured by ELISA. CD44 blocking with OS/37 was performed to investigate the mechanism of action of HA. Immunofluorescence cytochemistry confirmed binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose-dependently decreased expression of proinflammatory cytokine mRNAs and COX-2/PGE(2) production in IL-1-stimulated SSF. Pretreatment with OS/37 reversed the inhibitory effects of HA. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease.
Mitsui
Yasuhiro
Y
Department of Orthopedic Surgery, Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Gotoh
Masafumi
M
Nakama
Kenjirou
K
Yamada
Tetsu
T
Higuchi
Fujio
F
Nagata
Kensei
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017006:Rotator Cuff / Q000473:pathology*; D013585:Synovitis / Q000188:drug therapy* / Q000473:pathology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D012333:RNA, Messenger; D006820:Hyaluronic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone