Production of neuropeptide substance P by synovial fibroblasts from patients with rheumatoid arthritis and osteoarthritis.
We examined the production of substance P (SP) in synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression of beta-preprotachykinin-A (beta-PPT-A) mRNA was confirmed by reverse transcription-polymerase chain reaction analysis. SP contents in culture medium were increased by treatment of RA fibroblasts with transforming growth factor-beta (TGFbeta) (10 ng/ml). Levels of SP release were elevated at 12 h after TGFbeta stimulation whereas the expression of beta-PPT-A mRNA was enhanced at 3 h. Furthermore, SP production in response to TGFbeta was dose-dependently enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also significantly released SP in the presence of TGFbeta (10 ng/ml) plus bFGF (50 ng/ml). These results suggest that SP produced by synovial fibroblasts may participate in joint diseases.
Inoue
H
H
Research Laboratory, Minophagen Pharmaceutical Co., 2-2-3, Komatsubara, Zama-shi, 228-0002, Kanagawa, Japan. h_inoue@mx6.mesh.ne.jp
Shimoyama
Y
Y
Hirabayashi
K
K
Kajigaya
H
H
Yamamoto
S
S
Oda
H
H
Koshihara
Y
Y
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D015320:Tachykinins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; D016212:Transforming Growth Factor beta; C044206:preprotachykinin; D016222:Fibroblast Growth Factor 2; D013373:Substance P