Vitamin D Immune Modulatory Effect on the Anti-inflammatory potential of HDL Associated Proteins

Abstract

Introduction: Vitamin D deficiency is highly prevalent in Qatar. Vitamin D exerts immune-modulatory effects leading to reduced inflammation. Therefore, vitamin D deficiency is associated with increased subclinical inflammation. vitamin D deficiency associated with dyslipidemia. HDL possesses anti-inflammatory properties, and neutralizes endotoxin (LPS). Therefore it is an anti-inflammatory modulator during sepsis and inflammation. We suggest that HDL and the associated proteins ApoM, ApoD, ApoA-1, and LL-37 are playing an important role in LPS detoxification process, by clearing the endotoxins and minimizing the cytokines released. The nature of the relationship between HDL and associated proteins and vitamin D and their role in endotoxins clearance is not fully understood. Methodology: The study is designed to have two arms. Translational arm focusing on the nature of the association between vitamin D deficiency, dyslipidemia, inflammation, HDL, and HDL- associated proteins ApoM, ApoD, AopA-1, and LL-37 in healthy adults, and identifying the modifications of proteomic and metabolomic profile during vitamin D and dyslipidemia. In vitro studies investigated the anti-inflammatory potential of HDL-associated proteins, including identifying the relationship between vitamin D levels and HDL-associated proteins ApoM, ApoD, ApoA-1, and LL-37 expression in THP1 using PCR, and ELISA. Determining the role of ApoM in endotoxin neutralization using molecular docking simulations of ApoM - E. coli LPS, isothermal titration calorimetry (ITC), and measuring the TNF-?, nitric oxide release in THP1 cells. Rationale of the study: This research will enhance understanding of the mechanistic physiology associated proteins during inflammation and will illustrate the clinical correlation of HDL-associated proteins to VitD deficiency. Therefore, will facilitate the therapeutic design of engineered functional HDL particles for potential use in sepsis. Result and conclusion Vitamin D deficiency is inversely associate with subclinical inflammation marker monocyte percentage to HDL ratio (MHR). Alterations in sphingomyelins are observed in participants with combined vitamin D deficiency and dyslipidemia. Also, enrichment of inflammation and cancer pathways is revealed by proteomics analysis. Vitamin D deficiency affected HDL-associated proteins expression and impacted the anti-inflammatory potential of HDL. ApoM binds endotoxin with high affinity and contributes to neutralization and clearance by HDL. Vitamin D modulated the expression of HDL-associated apolipoproteins ApoA-1 and ApoM in monocytes.