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The Journal of steroid biochemistry and molecular biology
Sep, 2014;143 183-91.

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

Malcolm B Lowry, Chunxiao Guo, Niels Borregaard, Adrian F Gombart
Author Information
  1. Malcolm B Lowry: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA.
  2. Chunxiao Guo: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
  3. Niels Borregaard: Department of Hematology, Rigshospitalet-4042, University of Copenhagen, Copenhagen DK-1200, Denmark.
  4. Adrian F Gombart: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address: adrian.gombart@oregonstate.edu.
PMID: 24565560 DOI: 10.1016/j.jsbmb.2014.02.004

Abstract

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.

Keywords

Dendritic cells LL-37 Macrophage Osteoclasts Parathyroid hormone hCAP18

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Grants

  1. R01 AI065604/NIAID NIH HHS
  2. 5R01AI065604/NIAID NIH HHS

MeSH Term

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Blotting, Western
Cathelicidins
Cells, Cultured
Dendritic Cells
Flow Cytometry
Gene Expression Regulation
Humans
Macrophages
Monocytes
Neutrophils
Osteoclasts
Parathyroid Hormone
RNA, Messenger
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Vitamin D

Chemicals

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Cathelicidins
Parathyroid Hormone
RNA, Messenger
dihydroxy-vitamin D3
Vitamin D
Journal Article Research Support, N.I.H., Extramural

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