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Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway.
Int J Mol Sci 2017; 18(4)IJ

Abstract

Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases.

Authors+Show Affiliations

Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. haijsunjiangnan@jiangnan.edu.cn.Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. baojiangexz@sina.com.Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. hlxuzhou11@sina.com.Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. qiulydoc@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28420166

Citation

Sun, Haijian, et al. "Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation Via Regulation of TLR4 and PPAR-γ Dependent On PI3K/Akt/mTOR Signal Pathway." International Journal of Molecular Sciences, vol. 18, no. 4, 2017.
Sun H, Zhu X, Cai W, et al. Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway. Int J Mol Sci. 2017;18(4).
Sun, H., Zhu, X., Cai, W., & Qiu, L. (2017). Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway. International Journal of Molecular Sciences, 18(4), doi:10.3390/ijms18040844.
Sun H, et al. Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation Via Regulation of TLR4 and PPAR-γ Dependent On PI3K/Akt/mTOR Signal Pathway. Int J Mol Sci. 2017 Apr 17;18(4) PubMed PMID: 28420166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway. AU - Sun,Haijian, AU - Zhu,Xuexue, AU - Cai,Weiwei, AU - Qiu,Liying, Y1 - 2017/04/17/ PY - 2017/02/27/received PY - 2017/04/11/revised PY - 2017/04/13/accepted PY - 2017/4/20/entrez PY - 2017/4/20/pubmed PY - 2017/7/1/medline KW - LPS KW - PPAR-γ KW - TLR4 KW - endothelial cells KW - inflammation JF - International journal of molecular sciences JO - Int J Mol Sci VL - 18 IS - 4 N2 - Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/28420166/Hypaphorine_Attenuates_Lipopolysaccharide_Induced_Endothelial_Inflammation_via_Regulation_of_TLR4_and_PPAR_γ_Dependent_on_PI3K/Akt/mTOR_Signal_Pathway_ L2 - http://www.mdpi.com/resolver?pii=ijms18040844 DB - PRIME DP - Unbound Medicine ER -