25-Hydroxyvitamin D potentializes extracellular cathelicidin release from human PBMC stimulated ex vivo with either bacterial (LPS) or viral (P: IC) mimetics.

Autor: Aldekwer S; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Goncalves-Mendes N; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Bingula R; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Martinroche G; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Lanchais K; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Rougé S; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Farges MC; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Rossary A; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Diab-Assaf M; Faculty of Sciences II, Lebanese University, Fanar, Lebanon., Vasson MP; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France., Talvas J; UMR 1019 Human Nutrition Unit, INRAe, University of Clermont Auvergne, CRNH Auvergne, 63000, Clermont-Ferrand, France. Jeremie.talvas@uca.fr.
Jazyk: angličtina
Zdroj: Journal of physiology and biochemistry [J Physiol Biochem] 2022 May; Vol. 78 (2), pp. 335-342. Date of Electronic Publication: 2022 Jan 05.
DOI: 10.1007/s13105-021-00868-z
Abstrakt: Human cathelicidin refers to the cationic antimicrobial peptide hCAP18/LL-37. LL-37 is formed by cleavage of the propeptide hCAP18 coded by the CAMP gene. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)D), has been shown to induce the CAMP gene expression through promoter activation. We previously failed to demonstrate in a clinical trial that supplementation of 25-hydroxyvitamin D (25(OH)D) improves LL-37 serum levels. The aim of this work was to evaluate the impact of 25(OH)D supplementation on intracellular expression of CAMP and secretion of LL-37 in an ex vivo model using the peripheral blood mononuclear cells (PBMC). PBMC collected from healthy donors and incubated with different concentrations of 25(OH)D (0 ng/ml: control (D0); 25 ng/ml: deficient (D25); 75 ng/ml: physiological (D75); 125 ng/ml: supraphysiological (D125)) were stimulated or not with lipopolysaccharide (LPS, 100 ng/ml) or synthetic double-stranded RNA Poly (I: C) (PIC, 10 µg/ml). The intracellular expressions of the CAMP gene and the hCAP18 peptide were measured respectively after 24-h and 48-h incubation periods. The concentration of LL-37 was determined in the culture medium after 48-h incubation. 25(OH)D significantly induced CAMP gene expression at 24 h with a maximum effect at a dose of D125 in either unstimulated (tenfold expression) or stimulated (LPS: 100-fold expression; PIC: 15-fold expression) conditions. Intracellular hCAP18 peptide was overexpressed at 48 h under unstimulated (1.5-fold, D125) and stimulated conditions, LPS (twofold, D125) and PIC (2.5-fold, D125). The secretion of LL-37 in the culture medium was significantly induced by 25(OH)D only in both stimulated (LPS and PIC) conditions in a dose-dependent manner. Our results demonstrate that 25(OH)D incubation increases intracellular expression of CAMP and hCAP18, but extracellular secretion of LL-37 antimicrobial peptide is increased by 25(OH)D only when PBMC from healthy donors were stimulated with bacterial or viral immune mimetic.
(© 2022. The Author(s) under exclusive licence to University of Navarra.)
Databáze: MEDLINE
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