Abstract
Bee venom (BV) has been used in patients with rheumatoid arthritis, a condition characterized by rheumatoid joint destruction mediated, in large part, by matrix metalloproteinases (MMPs). We investigated the effects of melittin, a major component of bee venom, on the production of MMPs in human rheumatoid arthritic fibroblast-like synoviocytes (FLS). Lipopolysaccharide (LPS)-stimulated MMP3 production was significantly inhibited by melittin, which also inhibited LPS-induced DNA binding by nuclear factor kappaB (NF-kappaB). Mellitin had no effect on IL-1beta- or TNF-alpha-induced MMP1 or MMP3 production and did not decrease LPS-induced secretion of MMP1. Taken together, these findings suggest that melittin may exert its anti-rheumatoid effects, at least in part, by inhibiting MMP3 production, most likely through inhibition of NF-kappaB activity.
MeSH terms
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Aged
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Aged, 80 and over
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Antirheumatic Agents / pharmacology*
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Antirheumatic Agents / therapeutic use
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Arthritis, Rheumatoid / drug therapy*
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Arthritis, Rheumatoid / enzymology
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Arthritis, Rheumatoid / pathology
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Fibroblasts / drug effects*
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Fibroblasts / enzymology
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Fibroblasts / pathology
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Humans
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Interleukin-1beta / metabolism
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Lipopolysaccharides / pharmacology
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Matrix Metalloproteinase 1 / metabolism*
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Matrix Metalloproteinase 3 / metabolism*
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Melitten / pharmacology*
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Melitten / therapeutic use
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Middle Aged
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NF-kappa B / metabolism
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Synovial Membrane / drug effects*
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Synovial Membrane / enzymology
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Synovial Membrane / pathology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antirheumatic Agents
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Interleukin-1beta
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Lipopolysaccharides
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NF-kappa B
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Tumor Necrosis Factor-alpha
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Melitten
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MMP3 protein, human
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 1