Luteolin inhibits proliferation and affects the function of stimulated rat synovial fibroblasts.
Hyperproliferation of synovial fibroblasts is considered to be a pivotal event in the pathogenesis of rheumatoid arthritis (RA). Luteolin, a flavonoid, inhibits the proliferation of synovial fibroblasts in collagen-induced arthritic rats. Treatment with luteolin also decreases the secretion of matrix metalloprotease-1 and -3 and the expression of IL-6, IL-8, IL-15, and TGF-beta. Luteolin treatment caused a delay of cells in the G(2)/M phase. Interestingly, combination treatment with luteolin and TNF-alpha exhibited a synergistic inhibitory effect in all experiments. Western blotting demonstrated that treatment with luteolin alone or combined with TNF-alpha inhibited the MAPK/ERKs and PI3K-Akt pathways. These results indicate that luteolin inhibits the proliferation and partially blocks the pathogenic function of synovial fibroblasts in rheumatoid arthritis.
Hou
Yanan
Y
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Room 901, Cell Biology Building, 320 Yueyang Road, Shanghai 200031, China.
Wu
Jiacai
J
Huang
Qin
Q
Guo
Lihe
L
D000818:Animals; D002455:Cell Division; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D016195:G2 Phase; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D013583:Synovial Membrane / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D020782:Matrix Metalloproteinases; D047311:Luteolin