Effects of melittin on the production of matrix metalloproteinase-1 and -3 in rheumatoid arthritic fibroblast-like synoviocytes.
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.
Nah
Seong-Su
SS
Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Ha
Eunyoung
E
Mun
Se Hwan
SH
Won
Hye-Jin
HJ
Chung
Joo-Ho
JH
D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008555:Melitten / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018501:Antirheumatic Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008555:Melitten; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1