TY - JOUR

T1 - Regulation of the human cathelicidin antimicrobial peptide gene by 1α,25-dihydroxyvitamin D3 in primary immune cells

AU - Lowry, Malcolm B

AU - Guo, Chunxiao

AU - Borregaard, Niels

AU - Gombart, Adrian F

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/9

Y1 - 2014/9

N2 - Production of the human cathelicidin antimicrobial peptide gene (hCAP18/LL-37), is regulated by 1α,25-dihydroxyvitamin D3 (1,25D3) and is critical in the killing of pathogens by innate immune cells. In addition, secreted LL-37 binds extracellular receptors and modulates the recruitment and activity of both innate and adaptive immune cells. Evidence suggests that during infections activated immune cells locally produce increased levels of 1,25D3 thus increasing production of hCAP18/LL-37. The relative expression levels of hCAP18/LL-37 among different immune cell types are not well characterized. The aim of this study was to determine the relative levels of hCAP18/LL-37 in human peripheral blood immune cells and determine to what extent 1,25D3 increased its expression in peripheral blood-derived cells. We show for the first time, a hierarchy of expression of hCAP18 in freshly isolated cells with low levels in lymphocytes, intermediate levels in monocytes and the highest levels found in neutrophils. In peripheral blood-derived cells, the highest levels of hCAP18 following treatment with 1,25D3 were in macrophages, while comparatively lower levels were found in GM-CSF-derived dendritic cells and osteoclasts. We also tested whether treatment with parathyroid hormone in combination with 1,25D3 would enhance hCAP18 induction as has been reported in skin cells, but we did not find enhancement in any immune cells tested. Our results indicate that hCAP18 is expressed at different levels according to cell type and lineage. Furthermore, potent induction of hCAP18 by 1,25D3 in macrophages and dendritic cells may modulate functions of both innate and adaptive immune cells at sites of infection.

AB - Production of the human cathelicidin antimicrobial peptide gene (hCAP18/LL-37), is regulated by 1α,25-dihydroxyvitamin D3 (1,25D3) and is critical in the killing of pathogens by innate immune cells. In addition, secreted LL-37 binds extracellular receptors and modulates the recruitment and activity of both innate and adaptive immune cells. Evidence suggests that during infections activated immune cells locally produce increased levels of 1,25D3 thus increasing production of hCAP18/LL-37. The relative expression levels of hCAP18/LL-37 among different immune cell types are not well characterized. The aim of this study was to determine the relative levels of hCAP18/LL-37 in human peripheral blood immune cells and determine to what extent 1,25D3 increased its expression in peripheral blood-derived cells. We show for the first time, a hierarchy of expression of hCAP18 in freshly isolated cells with low levels in lymphocytes, intermediate levels in monocytes and the highest levels found in neutrophils. In peripheral blood-derived cells, the highest levels of hCAP18 following treatment with 1,25D3 were in macrophages, while comparatively lower levels were found in GM-CSF-derived dendritic cells and osteoclasts. We also tested whether treatment with parathyroid hormone in combination with 1,25D3 would enhance hCAP18 induction as has been reported in skin cells, but we did not find enhancement in any immune cells tested. Our results indicate that hCAP18 is expressed at different levels according to cell type and lineage. Furthermore, potent induction of hCAP18 by 1,25D3 in macrophages and dendritic cells may modulate functions of both innate and adaptive immune cells at sites of infection.

KW - Anti-Bacterial Agents

KW - Blotting, Western

KW - Cathelicidins

KW - Cells, Cultured

KW - Dendritic Cells

KW - Flow Cytometry

KW - Gene Expression Regulation

KW - Humans

KW - Macrophages

KW - Monocytes

KW - Neutrophils

KW - Osteoclasts

KW - Parathyroid Hormone

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Vitamin D

U2 - 10.1016/j.jsbmb.2014.02.004

DO - 10.1016/j.jsbmb.2014.02.004

M3 - Journal article

C2 - 24565560

VL - 143

SP - 183

EP - 191

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

ER -