Melittin has a chondroprotective effect by inhibiting MMP-1 and MMP-8 expressions via blocking NF-kappa B and AP-1 signaling pathway in chondrocytes

Title
Melittin has a chondroprotective effect by inhibiting MMP-1 and MMP-8 expressions via blocking NF-kappa B and AP-1 signaling pathway in chondrocytes
Author(s)
장현욱정윤정[정윤정]신재문[신재문]배영석[배영석]조현지[조현지]박관규[박관규]채정윤[채정윤]한상미[한상미]문성관[문성관]김원제[김원제]최융현[최융현]김철호[김철호]장영채[장영채]
Keywords
HUMAN ARTICULAR CHONDROCYTES; NECROSIS-FACTOR-ALPHA; BEE VENOM; RHEUMATOID-ARTHRITIS; MATRIX METALLOPROTEINASES; INFLAMMATORY ARTHRITIS; GENE-EXPRESSION; DOWN-REGULATION; IN-VITRO; ACTIVATION
Issue Date
201504
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL IMMUNOPHARMACOLOGY, v.25, no.2, pp.400 - 405
Abstract
Bee venom is a natural ingredient produced by the honey bee (Apis mellifera), and has been widely used in China, Korea and Japan as a traditional medicine for various diseases such as arthritis, rheumatism, and skin diseases However, the regulation of the underlying molecular mechanisms of the anti-arthritis by bee venom and its major peptides is largely unknown. In this study, we investigated the potential molecular mechanisms underlying the anti-arthritis effect of bee venom and its major peptides, melittin and apamin, in tumor necrosis factor-alpha (TNF-alpha) responsive C57BL/6 mice chondrocyte cells. The bee venom and melittin significantly and selectively suppressed the TNF-alpha-mediated decrease of type II collagen expression, whereas the apamin had no effects on the type II collagen expression. We, furthermore, found that the bee venom and melittin inhibited the protein expression of matrix metalloproteinase (MMP)-1 and MMP-8, which suggests that the chondroprotective effect of bee venom may be caused by melittin. The inhibitory effects of melittin on the TNF-alpha-induced MMP-1 and MMP-8 protein expression were regulated by the inhibition of NF-kappa B and AP-1. In addition, melittin suppressed the TNF-alpha-induced phosphorylation of Akt, JNK and ERK1/2, but did not affect the phosphorylation of p38 kinase. These results suggest that melittin suppresses TNF-alpha-stimulated decrease of type II collagen expression by the inhibiting MMP-1 and MMP-8 through regulation of the NF-kappa B and AP-1 pathway and provision of a novel role for melittin in anti-arthritis action. (C) 2015 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/32830http://dx.doi.org/10.1016/j.intimp.2015.02.021
ISSN
1567-5769
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약학대학 > 약학부 > Articles
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