Triple Inhibitory Activity of Cliona celata Against TNF-alpha-Induced Matrix Metalloproteinase-9 Production Via Downregulated NF-kappa B and AP-1, Enzyme Activity, and Migration Potential

Title
Triple Inhibitory Activity of Cliona celata Against TNF-alpha-Induced Matrix Metalloproteinase-9 Production Via Downregulated NF-kappa B and AP-1, Enzyme Activity, and Migration Potential
Author(s)
장현욱서석종곽충환[곽충환]송권호[송권호]권경민[권경민]정태욱[정태욱]조성학[조성학]김연규[김연규]윤호동[윤호동]이영춘[이영춘]김동수[김동수]박성재[박성재]나민균손종근김철호[김철호]
Keywords
SMOOTH-MUSCLE-CELLS; MULTIPLE SIGNALING PATHWAYS; MATRIX METALLOPROTEINASES; TISSUE INHIBITORS; ARTERIAL INJURY; EXPRESSION; ACTIVATION; GROWTH; HASMC; MMP-9
Issue Date
201204
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
INFLAMMATION, v.35, no.2, pp.736 - 745
Abstract
Extracellular matrix-degrading protease, matrix metalloproteinase-9 (MMP-9), is known to be involved in vascular smooth muscle cell (SMC)'s aberrant proliferation and movement in atherosclerotic lesions. During screening of the MMP-9-inhibitory compounds from marine animal resources, we have found that the ethyl acetate extract from Cliona celata (ECC) effectively inhibits the SMC-derived MMP-9 enzyme activity and gene expression. In addition, the ECC effectively repressed the migration potential of the tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic smooth muscle cell (HASMC). As assessed by Western blot analysis, the produced MMP-9 protein levels in the TNF-alpha-induced HASMC were significantly decreased by the concomitant treatment of ECC at the 50- to 300-mu g/mL concentration ranges. In addition, in the RT-PCR experiment, the expressed MMP-9 mRNA levels in the TNF-alpha-induced HASMC were seemingly decreased by ECC treatment at the same concentration ranges (50-300 mu g/mL). For the action mechanism(s) of ECC to the phenotype changes in HASMC, we have further evaluated the ECC's pharmacological activities on the signal molecules which are importantly linked in the MMP-9 expression and cell migration potential of HASMC. We have found that extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation as a target point is suppressed by the ECC treatment in the TNF-alpha-treated HASMC. Using electrophoretic mobility shift assay, the nuclear extracts purified from ECC-treated HASMCs were shown to decrease the binding potentials on the labeled nuclear factor-kappaB (NF-kappa B) and activator protein 1 probes. NF-kappa B p65 and phosphorylated c-Jun contents were also decreased in the purified nuclear extracts from the ECC-treated HASMC, as confirmed by Western blot analysis. Finally, it was shown that the ECC-treated HASMCs were less migrated when compared to the TNF-alpha-treated cells, as confirmed by HASMC migration assays using the 8-mu m pore transwell membranes. From these results, it was proposed that ECC has a potentially applicable anti-atherosclerotic activity.
URI
http://hdl.handle.net/YU.REPOSITORY/28690http://dx.doi.org/10.1007/s10753-011-9369-6
ISSN
0360-3997
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약학대학 > 약학부 > Articles
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