GPR40/FFA1 and neutral sphingomyelinase are involved in palmitate-boosted inflammatory response of microvascular endothelial cells to LPS

Atherosclerosis
Zhongyang LuYan Huang

Abstract

Increased levels of both saturated fatty acids (SFAs) and lipopolysaccharide (LPS) are associated with type 2 diabetes. However, it remains largely unknown how SFAs interact with LPS to regulate inflammatory responses in microvascular endothelial cells (MIC ECs) that are critically involved in atherosclerosis as a diabetic complication. In this study, we compared the effects of LPS, palmitic acid (PA), the most abundant saturated fatty acid, or the combination of LPS and PA on interleukin (IL)-6 expression by MIC ECs and explored the underlying mechanisms. Human cardiac MIC ECs were treated with LPS, PA and LPS plus PA and the regulatory pathways including receptors, signal transduction, transcription and post-transcription, and sphingolipid metabolism for IL-6 expression were investigated. G protein-coupled receptor (GPR)40 or free fatty acid receptor 1 (FFA1), but not toll-like receptor 4, was involved in PA-stimulated IL-6 expression. PA not only stimulated IL-6 expression by itself, but also remarkably enhanced LPS-stimulated IL-6 expression via a cooperative stimulation on mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, and both transcriptional and post-transcriptional activation. Furthermor...Continue Reading

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Citations

May 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Tom LallemandNathalie Augé
Jul 17, 2019·Clinical Science·Jean-François ThibodeauLyne Gagnon
Jul 11, 2018·American Journal of Physiology. Endocrinology and Metabolism·Yanchun LiYan Huang
Jan 31, 2020·British Journal of Pharmacology·Michelangelo CertoClaudio Mauro
Aug 1, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jan Korbecki, Karolina Bajdak-Rusinek
May 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hongjiao XiangTao Wu
Jul 8, 2021·Clinical Science·Timothy M Palmer, Ian P Salt

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