Inflammatory cytokines induced down-regulation of m-calpain mRNA expression in fibroblastic synoviocytes from patients with osteoarthritis and rheumatoid arthritis.
Our previous reports revealed that calpain has proteoglycanase activity and exists in synovial fluid in osteoarthritis and rheumatoid arthritis. We examined the effects of cytokines on expression of the calpain-calpastatin system in fibroblastic synoviocytes (FLS). Primary cultures of human FLS from osteoarthritis (OA) and rheumatoid arthritis (RA) patients were stimulated with inflammatory cytokines and the amounts of m-calpain and calpastatin mRNAs expressed were determined by Northern blotting. Northern blots were subjected to computerized densitometer and band intensities were determined. Interleukin-1 (IL-1) down-regulated m-calpain and tissue-type calpastatin mRNA expression in OA and RA FLS. In RA FLS, although IL-6 did not alter m-calpain mRNA expression, IL-1 + tumor necrosis factor (TNF) and IL-1 + transforming growth factor (TGF) down-regulated m-calpain mRNA expression. These results provide new information about the effects of inflammatory cytokines on calpain and calpastatin system in OA and RA pathology.
Ishikawa
H
H
Department of Orthopaedic Surgery, Faculty of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Nakagawa
Y
Y
Shimizu
K
K
Nishihara
H
H
Matsusue
Y
Y
Nakamura
T
T
D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D010003:Osteoarthritis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013582:Synovial Fluid / Q000166:cytology; D015291:Transforming Growth Factors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; C033668:calpastatin; D002154:Calpain