Autophagy efficacy and vitamin D status: Population effects

•The efficacy of the autophagic response is shaped by 25(OH)D3, which is population specific.•1,25(OH)2D3 supplementation enhances autophagy under 25(OH)D3 deficient circumstances.•Supplementation under 25(OH)D3 sufficient circumstances does not benefit the autophagic response. Toll-like receptor (T...

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Veröffentlicht in:Cellular immunology 2020-06, Vol.352, p.104082-104082, Article 104082
Hauptverfasser: Abhimanyu, Meyer, Vanessa, Jones, Brandon R., Bornman, Liza
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container_title Cellular immunology
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Meyer, Vanessa
Jones, Brandon R.
Bornman, Liza
description •The efficacy of the autophagic response is shaped by 25(OH)D3, which is population specific.•1,25(OH)2D3 supplementation enhances autophagy under 25(OH)D3 deficient circumstances.•Supplementation under 25(OH)D3 sufficient circumstances does not benefit the autophagic response. 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 
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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 &lt; 0.010), but higher Beclin1, VDR, IL6 and TNFA (P &lt; 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). 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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 &lt; 0.010), but higher Beclin1, VDR, IL6 and TNFA (P &lt; 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.</description><subject>Adult</subject><subject>African</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Autophagy - physiology</subject><subject>Beclin1</subject><subject>Calcitriol - blood</subject><subject>Calcitriol - metabolism</subject><subject>Calcitriol - physiology</subject><subject>Chromatography, Liquid - methods</subject><subject>Female</subject><subject>Humans</subject><subject>LC3-IIB</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Middle Aged</subject><subject>Monocytes - metabolism</subject><subject>Pam3CSK4</subject><subject>Population-specific</subject><subject>Primary Cell Culture</subject><subject>Receptors, Calcitriol - genetics</subject><subject>Receptors, Calcitriol - metabolism</subject><subject>South Africa</subject><subject>Tandem Mass Spectrometry - methods</subject><subject>TLR2/1</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-Like Receptors - genetics</subject><subject>Toll-Like Receptors - metabolism</subject><subject>VDR</subject><subject>Vitamin D</subject><subject>Vitamin D - metabolism</subject><subject>Vitamin D - physiology</subject><issn>0008-8749</issn><issn>1090-2163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PwzAMhiMEgjH4CaAeuXQ4SdOmcEDT-JQmwQHOUZq4kKlfNO2k_XtadXDlZMl-bOt9CLmgsKBA4-vNwmBRuLJcMGBjLwLJDsiMQgohozE_JDMAkKFMovSEnHq_AaA0SuGYnHDGIio4zMjtsu_q5kt_7gLMc2e02QW6ssHWdbp0VXAf-E53vb8J3uqmL3Tn6mok0XT-jBzluvB4vq9z8vH48L56DtevTy-r5To0PBZdGGcQZ0ZYzJEyJoWFlCHLhdAy4zROIEryCFEwKqzJLGjNs2EcSUZB5jHlc3I13W3a-rtH36nS-TG9rrDuvWJcxixJOYyomFDT1t63mKumdaVud4qCGr2pjdp7U6M3NXkb9i73L_qsRPu39StqAO4mAIegW4et8sZhZdC6dnChbO3-efED-MF_4Q</recordid><startdate>202006</startdate><enddate>202006</enddate><creator>Abhimanyu</creator><creator>Meyer, Vanessa</creator><creator>Jones, Brandon R.</creator><creator>Bornman, Liza</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202006</creationdate><title>Autophagy efficacy and vitamin D status: Population effects</title><author>Abhimanyu ; 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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 &lt; 0.010), but higher Beclin1, VDR, IL6 and TNFA (P &lt; 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.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>32241530</pmid><doi>10.1016/j.cellimm.2020.104082</doi><tpages>1</tpages></addata></record>
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subjects Adult
African
Autophagy
Autophagy - drug effects
Autophagy - physiology
Beclin1
Calcitriol - blood
Calcitriol - metabolism
Calcitriol - physiology
Chromatography, Liquid - methods
Female
Humans
LC3-IIB
Male
Microtubule-Associated Proteins - genetics
Middle Aged
Monocytes - metabolism
Pam3CSK4
Population-specific
Primary Cell Culture
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
South Africa
Tandem Mass Spectrometry - methods
TLR2/1
Toll-Like Receptor 2
Toll-Like Receptors - genetics
Toll-Like Receptors - metabolism
VDR
Vitamin D
Vitamin D - metabolism
Vitamin D - physiology
title Autophagy efficacy and vitamin D status: Population effects
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