Carpinus truczaninowii extract showed anti-inflammatory response on human aortic vascular smooth muscle cells

Inflammation of the arterial wall is critical to atherosclerosis pathogenesis. The switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells is essential in the exacerbation of vascular inflammation. Platonin, a cyanine photosensitizing dye, exhibits protective effects in sepsis, trauma, and acute ischemic stroke through its anti-inflammatory capacity in macrophages. The present study investigated the effects and underlying mechanisms of platonin in inflammatory VSMCs. Pretreatment with platonin suppressed the expression of inducible nitric oxide synthetase and mature interleukin-1β but not that of monocyte chemoattractant protein-1 (MCP-1) in VSMCs stimulated by a combination of lipopolysaccharide and interferon-γ (LPS/IFN-γ). Furthermore, platonin inhibited LPS/IFN-γ-induced Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation though the direct reduction of p65Ser536 phosphorylation but not the restoration of Inhibitor of nuclear factor kappa B (IκBα) degradation in VSMCs. However, platonin inhibited Oxidized low-density lipoprotein (ox-LDL)-induced MCP-1 production, possibly through the attenuation of Activator protein 1 (AP-1) binding activity and C-Jun N-terminal kinases ½ (JNK1/2) phosphorylation. Platonin also lowered lipid drop accumulation in VSMCs in Oil red O staining assay. The results collectively indicated that platonin has a vascular protective property with potent anti-inflammatory effects in VSMCs. In conclusion, platonin should be a potential for treating vascular inflammatory diseases such as atherosclerosis.

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17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Journal of Molecular Endocrinology ◽

10.1677/jme-09-0166 ◽

2010 ◽

Vol 45 (2) ◽

pp. 87-97 ◽

Cited By ~ 22

Author(s):

Ping Jiang ◽

Jinwen Xu ◽

Shuhui Zheng ◽

Jinghe Huang ◽

Qiuling Xiang ◽

...

Keyword(s):

Smooth Muscle ◽

Cell Migration ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

P38 Mapk ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Pyrrolidine Dithiocarbamate ◽

17Β Estradiol ◽

Anti Inflammatory

Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) triggers the release of inflammatory cytokines that accelerate its initiation and progression. Estrogen has been proven to be vasoprotective against atherosclerosis; however, the anti-inflammatory function of estrogen in the vascular system remains obscure. In this study, we investigated the effect of estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS significantly enhances MCP-1 production and this is dependent on nuclear factor κ B (NFκB) signaling, since the use of NFκB inhibitor pyrrolidine dithiocarbamate or the silencing of NFκB subunit p65 expression with specific siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 17β-estradiol (E2) inhibits LPS-induced MCP-1 production in a time- and dose-dependent manner, which is related to the suppression of p65 translocation to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while E2 markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 translocation to nucleus and MCP-1 production, suggesting that E2 suppresses NFκB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a major role as an autocrine factor in atherosclerosis. In addition, E2 inhibits LPS-promoted cell migration by downregulation of MCP-1 production. Overall, our results demonstrate that E2 exerts anti-inflammatory property antagonistic to LPS in VSMCs by reducing MCP-1 production, and this effect is related to the inhibition of p38 MAPK/NFκB cascade.

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Abstract 381: IL-19 Inhibits Atherosclerosis in LDLR-/- Mice by Modulating Cholesterol Uptake in Macrophages and Vascular Smooth Muscle Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a381 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Khatuna Gabunia ◽

Stephen P Ellison ◽

James M Richards ◽

Sheri E Kelemen ◽

Michael V Autieri

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Atherosclerotic Plaque ◽

Scavenger Receptor ◽

Muscle Cells ◽

Wild Type ◽

Anti Inflammatory ◽

M2 Phenotype

IL-19 is a recently described, putative anti-inflammatory cytokine which had previously been ascribed to be leukocyte specific. IL-19 is not detected in normal artery, but we detected IL-19 in multiple cell types in human atherosclerotic plaque suggesting a role for this interleukin in atherosclerosis. The purpose of this study was to determine whether administration of exogenous IL-19 could attenuate development of pre-formed atherosclerotic plaque, and to identify potential molecular mechanisms. LDLR-/- mice were fed high-fat diet for 12 weeks and then administered with 10ng/g/day IL-19 or PBS for an additional 8 weeks. En face analysis demonstrated that IL-19 could halt, but not reverse existing plaque (26.7+/-1.7%, 41.03+/-3.1%, 23.70+/-2.6% for baseline, PBS control, and IL-19-treated mice). Foam cell formation by macrophages and vascular smooth muscle cells (VSMC) is a hallmark event during atherosclerosis. Nothing has been reported regarding IL-19 effects on macrophage or VSMC lipid uptake; we therefore investigated whether IL-19 affects macrophage and VSMC cholesterol handling. Addition of IL-19 to wild-type bone marrow derived macrophages (BMDM) significantly promoted oxLDL uptake, conversely, BMDM from IL-19-/- mice had significantly less oxLDL uptake compared to wild-type BMDM. Addition of IL-19 to wild type BMDM significantly increased expression of scavenger receptor B1 (SR-B1), and decreased expression of inflammatory cytokines TNFα, IL-12b, MCP1. Interestingly, converse results were obtained with VSMC, as addition of IL-19 to wild-type VSMC decreased uptake of oxLDL ( p<0.05 ) and decreased expression of scavenger receptor CD36. VSMC isolated from IL-19-/- mice had increased uptake of oxLDL (p<0.0001). It is reported that M2 macrophages participate in plaque regression. IL-19 decreased IL-12b and significantly promoted the polarization of anti-inflammatory M2 phenotype in BMDM as evidenced by the increased expression of YM1 and IL-10 mRNA. These data demonstrate that IL-19 can inhibit progression of existing atherosclerotic plaque by modulating lipid metabolism in VSMC and macrophages and by promoting macrophage differentiation into an alternative, anti-inflammatory M2 phenotype.

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