AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis.

Carla Dahlem,Dalei Wu,Yi He,Thomas Haarmann-Stemmann,Christoph F A Vogel,Sarah Y Kado,Norman Y Kado,Keith Bein

doi:10.3390/ijms21218287

Carla Dahlem, Dalei Wu + Show 6 more

Open Access

PDF Available

https://doi.org/10.3390/ijms21218287

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

There is strong evidence that exposure to fine particulate matter (PM2.5) and a high-fat diet (HFD) increase the risk of mortality from atherosclerotic cardiovascular diseases. Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. Here we investigate the effects of components of a HFD on PM-mediated activation of AHR in macrophages. Cells were treated with components of a HFD and AHR-activating PM and the expression of biomarkers of vascular inflammation was analyzed. The results show that glucose and triglyceride increase AHR-activity and PM2.5-mediated induction of cytochrome P450 (CYP)1A1 mRNA in macrophages. Cholesterol, fructose, and palmitic acid increased the PM- and AHR-mediated induction of proinflammatory cytokines in macrophages. Treatment with palmitic acid significantly increased the expression of inflammatory cytokines and markers of vascular injury in human aortic endothelial cells (HAEC) after treatment with PM2.5. The PM2.5-mediated activation of the atherogenic markers C-reactive protein (CRP) and S100A9, a damage-associated molecular pattern molecule, was found to be AHR-dependent and involved protein kinase A (PKA) and a CCAAT/enhancer-binding protein (C/EBP) binding element. This study identified nutritional factors interacting with AHR signaling and contributing to PM2.5-induced markers of atherogenesis and future cardiovascular risk.

Highlights

The Aryl Hydrocarbon Receptor (AHR) is known to mediate the toxicity of environmental pollutants such as dioxins and dioxin-like compounds
Recent studies including our work implicate the interaction of PM2.5 collected in an urban area (Sacramento, CA) with AHR as a key event leading to elevated levels of pro-inflammatory cytokines, such as IL-1β, IL-8, C-C motif chemokine ligand (CCL) and C-X-C motif chemokine ligand (CXCL) chemokines associated with the promotion of Th17-immune responses [7,20,21]
The cells were treated for 24 h with the potent AHR ligand TCDD or with PM2.5 collected from a major freeway tunnel system in Northern California as described under Materials and Methods

Summary

Introduction

The Aryl Hydrocarbon Receptor (AHR) is known to mediate the toxicity of environmental pollutants such as dioxins and dioxin-like compounds. AHR-dependent activation of cytochrome P450 (CYP) 1A1 and inflammatory cytokines such as interleukin (IL)-8 and IL-1β after exposure to PM have been shown in different cell types as well as in in vivo [7,8,9,10,11,12,13]. Recent studies indicate that PAHs are major contributors to PM-mediated atherogenesis and AHR-induced toxicity [14,15,16,17,18,19]. The AHR-mediated foam cell formation was associated with increased levels of IL-1β in atherosclerotic plaques [23]. C-reactive protein (CRP) and S100A9, a damage-associated molecular pattern molecule, have been identified as critical biomarkers in vascular inflammation and plaque disruption [24,25]

Methods

Results

Conclusion