Autophagy efficacy and vitamin D status: Population effects

Abhimanyu; Vanessa Meyer; Brandon R Jones; Liza Bornman

doi:10.1016/j.cellimm.2020.104082

Autophagy efficacy and vitamin D status: Population effects

Cell Immunol. 2020 Jun:352:104082. doi: 10.1016/j.cellimm.2020.104082. Epub 2020 Feb 28.

Authors

Abhimanyu¹, Vanessa Meyer², Brandon R Jones³, Liza Bornman⁴

Affiliations

¹ Department of Biochemistry, University of Johannesburg, Auckland Park Kingsway Campus, PO Box 524, Auckland Park 2006, Gauteng, South Africa. Electronic address: abhimanyu.abhimanyu@uct.ac.za.
² Department of Biochemistry, University of Johannesburg, Auckland Park Kingsway Campus, PO Box 524, Auckland Park 2006, Gauteng, South Africa. Electronic address: vanessa.meyer@wits.ac.za.
³ Department of Biochemistry, University of Johannesburg, Auckland Park Kingsway Campus, PO Box 524, Auckland Park 2006, Gauteng, South Africa.
⁴ Department of Biochemistry, University of Johannesburg, Auckland Park Kingsway Campus, PO Box 524, Auckland Park 2006, Gauteng, South Africa. Electronic address: liza.bornman@up.ac.za.

PMID: 32241530
DOI: 10.1016/j.cellimm.2020.104082

Abstract

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D₃ of healthy South Africans (Black individuals n = 10, White individuals n = 10) was quantified by LC-MS/MS. Primary monocytes-macrophages were supplemented in vitro with 1,25(OH)₂D₃ and stimulated with the lipoprotein Pam₃CysSerLys₄. TLR2, VDR, hCAP18, Beclin1, LC3-IIB, cytokines and CYP24A1 mRNA were quantified by flow cytometry and RT-qPCR, respectively. Black individuals showed significantly lower overall cumulative LC3-IIB (P < 0.010), but higher Beclin1, VDR, IL6 and TNFA (P < 0.050) than White individuals. 1,25(OH)₂D₃ enhanced autophagic flux in monocytes-macrophages from Black individuals upon TLR2/1 stimulation and strengthened autophagy in 25(OH)D₃ deficient individuals (independent cohort, n = 20). These findings support population-directed vitamin D supplementation.

Keywords: African; Autophagy; Beclin1; LC3-IIB; Pam(3)CSK(4); Population-specific; TLR2/1; VDR; Vitamin D.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autophagy / drug effects
Autophagy / physiology*
Calcitriol / blood
Calcitriol / metabolism*
Calcitriol / physiology
Chromatography, Liquid / methods
Female
Humans
Male
Microtubule-Associated Proteins / genetics
Middle Aged
Monocytes / metabolism*
Primary Cell Culture
Receptors, Calcitriol / genetics
Receptors, Calcitriol / metabolism
South Africa
Tandem Mass Spectrometry / methods
Toll-Like Receptor 2
Toll-Like Receptors / genetics
Toll-Like Receptors / metabolism
Vitamin D / metabolism
Vitamin D / physiology

Substances

MAP1LC3B protein, human
Microtubule-Associated Proteins
Receptors, Calcitriol
TLR2 protein, human
Toll-Like Receptor 2
Toll-Like Receptors
VDR protein, human
Vitamin D
Calcitriol