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Vitamin D triggers hCAP18/LL-37 production : Implications for LL-37-induced human osteoblast cytotoxicity

Aidoukovitch, Alexandra LU ; Bankell, Elisabeth LU ; Svensson, Daniel LU and Nilsson, Bengt Olof LU orcid (2024) In Biochemical and Biophysical Research Communications 712-713.
Abstract

The human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells. The CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-37. It has previously been shown that vitamin D stimulates CAMP gene activity, but less information is available demonstrating that vitamin D also can increase hCAP18/LL-37 protein production. Here, we show with RT-qPCR that a physiological concentration of vitamin D (50 nM) enhances CAMP mRNA levels by about 170 times in human THP-1 monocyte cells. Stimulation with 50 nM vitamin D increases hCAP18/LL-37 protein contents 3–4 times in THP-1 cell lysates demonstrated by both dot blot analysis and ELISA applying two different... (More)

The human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells. The CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-37. It has previously been shown that vitamin D stimulates CAMP gene activity, but less information is available demonstrating that vitamin D also can increase hCAP18/LL-37 protein production. Here, we show with RT-qPCR that a physiological concentration of vitamin D (50 nM) enhances CAMP mRNA levels by about 170 times in human THP-1 monocyte cells. Stimulation with 50 nM vitamin D increases hCAP18/LL-37 protein contents 3–4 times in THP-1 cell lysates demonstrated by both dot blot analysis and ELISA applying two different hCAP18/LL-37 antibodies. Treatment with the proteasome inhibitor MG132 enhances hCAP18/LL-37 levels, suggesting that turnover of hCAP18/LL-37 protein is regulated by the proteasome. The hCAP18/LL-37 concentration in vitamin D-stimulated THP-1 cells corresponds to 1.04 μM LL-37. Interestingly, synthetic LL-37, at this concentration, reduces viability of human osteoblast-like MG63 cells, whereas the THP-1 cells are less sensitive as demonstrated by the MTT assay. In summary, we show that vitamin D enhances hCAP18/LL-37 production, and that this effect can be of physiological/pathophysiological relevance for LL-37-induced human osteoblast toxicity.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptide, Cathelicidin, Cytotoxicity, hCAP18/LL-37, Proteasome, Vitamin D
in
Biochemical and Biophysical Research Communications
volume
712-713
article number
149962
publisher
Elsevier
external identifiers
  • pmid:38642493
  • scopus:85190751714
ISSN
0006-291X
DOI
10.1016/j.bbrc.2024.149962
language
English
LU publication?
yes
id
efde0678-c1c7-4fb1-a941-4f4d2e7f586c
date added to LUP
2024-04-29 08:31:06
date last changed
2024-05-13 09:50:36
@article{efde0678-c1c7-4fb1-a941-4f4d2e7f586c,
  abstract     = {{<p>The human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells. The CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-37. It has previously been shown that vitamin D stimulates CAMP gene activity, but less information is available demonstrating that vitamin D also can increase hCAP18/LL-37 protein production. Here, we show with RT-qPCR that a physiological concentration of vitamin D (50 nM) enhances CAMP mRNA levels by about 170 times in human THP-1 monocyte cells. Stimulation with 50 nM vitamin D increases hCAP18/LL-37 protein contents 3–4 times in THP-1 cell lysates demonstrated by both dot blot analysis and ELISA applying two different hCAP18/LL-37 antibodies. Treatment with the proteasome inhibitor MG132 enhances hCAP18/LL-37 levels, suggesting that turnover of hCAP18/LL-37 protein is regulated by the proteasome. The hCAP18/LL-37 concentration in vitamin D-stimulated THP-1 cells corresponds to 1.04 μM LL-37. Interestingly, synthetic LL-37, at this concentration, reduces viability of human osteoblast-like MG63 cells, whereas the THP-1 cells are less sensitive as demonstrated by the MTT assay. In summary, we show that vitamin D enhances hCAP18/LL-37 production, and that this effect can be of physiological/pathophysiological relevance for LL-37-induced human osteoblast toxicity.</p>}},
  author       = {{Aidoukovitch, Alexandra and Bankell, Elisabeth and Svensson, Daniel and Nilsson, Bengt Olof}},
  issn         = {{0006-291X}},
  keywords     = {{Antimicrobial peptide; Cathelicidin; Cytotoxicity; hCAP18/LL-37; Proteasome; Vitamin D}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Vitamin D triggers hCAP18/LL-37 production : Implications for LL-37-induced human osteoblast cytotoxicity}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2024.149962}},
  doi          = {{10.1016/j.bbrc.2024.149962}},
  volume       = {{712-713}},
  year         = {{2024}},
}