Abstract
Background and Aim: Endothelial activation is characterized by excessive production of cytokines and chemokines as well as adhesion molecules expression which is involved in the development of atherosclerosis. The aim of our study is to investigate the effects of short chain fatty acids (SCFA) on lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNFα)-induced endothelial activation.Methods and Results: Human umbilical vein endothelial cells (HUVEC) were pre-treated with acetate (10 mM), butyrate (0.1 mM) or propionate (0.3 mM) for 1, 16, or 24 h and then stimulated with LPS (1 or 10 μg/ml) or TNFα (100 pg/ml or 1 ng/ml) for 6, 12, or 24 h. Cytokines in the supernatant were measured by ELISA. HUVEC were pre-treated with acetate (10 mM), butyrate (5 mM) or propionate (10 mM) for 24 h and then stimulated with LPS (1 μg/ml) or TNFα (1 ng/ml) for 8 h. The expression of the adhesion molecules intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was detected by flow cytometry. The human blood mononuclear cell adhesive level to HUVEC monolayer was measured. LPS and TNFα induced a significant increase in the release of interleukin-6 (IL-6) and IL-8. Acetate, butyrate and propionate reduced IL-6 and IL-8 levels and the magnitude was dependent on the incubation times. LPS or TNFα increased ICAM-1 and VCAM-1 expression. Pre-incubation with acetate had no effect. In contrast, butyrate and propionate decreased VCAM-1 expression in TNFα stimulated cells but showed no effects on ICAM-1 expression. Butyrate significantly inhibited the adhesion of mononuclear cells to an endothelial monolayer and propionate was less effective.Conclusion: SCFA, including acetate, butyrate and propionate, influenced LPS- or TNFα-induced endothelial activation by inhibiting the production of IL-6 and IL-8, and reducing the expression of VCAM-1 and subsequent cell adhesion. Results were dependent on the concentrations and pre-incubation time of each SCFA and stimulation time of LPS or TNFα.
Highlights
Vascular endothelial cells serve as an important barrier to sustain homeostasis by maintaining normal vascular tone and blood fluidity and low production and release of pro-/anti-inflammatory factors
The short chain fatty acids (SCFA) used in this experiment did not affect the nonstimulated cytokines level
For acetate a pre-incubation time of 1, 16, and 24 h was most effective with 12 h LPS/TNFα stimulation, whilst a 24 h pre-incubation time with 1, 16, and 24 h stimulation times were chosen for butyrate and propionate
Summary
Vascular endothelial cells serve as an important barrier to sustain homeostasis by maintaining normal vascular tone and blood fluidity and low production and release of pro-/anti-inflammatory factors. Endothelial activation is a well-established early step to cardiovascular risk factors and is involved in the development of atherosclerosis (Favero et al, 2014). Endothelial activation induced by lipopolysaccharide (LPS, endotoxin) and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) is characterized by increased inflammatory cytokine production and adhesion molecule expression (Hunt and Jurd, 1998) which are two important steps in the development of atherosclerosis (Yan et al, 2015). Endothelial activation is characterized by excessive production of cytokines and chemokines as well as adhesion molecules expression which is involved in the development of atherosclerosis. The aim of our study is to investigate the effects of short chain fatty acids (SCFA) on lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNFα)-induced endothelial activation
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