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Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α

Svensson, Daniel LU ; Nebel, Daniel LU ; Voss, Ulrikke LU ; Ekblad, Eva LU and Nilsson, Bengt Olof LU (2016) In Cell and Tissue Research p.1-10
Abstract

The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin... (More)

The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin keratinocytes (HaCaT cells). Gene analysis revealed that human skin biopsies expressed higher levels of both CAMP and RXRα mRNA than human gingival biopsies, whereas VDR and RXRβ transcript levels were similar in skin and gingiva. In HaCaT cells, treatment with 1,25D3 (5 nM and 1 μM) for 4 and 24 h up-regulated CAMP mRNA several fold, and treatment with 1,25D3 for 24 h increased protein expression of the pro-form of LL-37 (hCAP-18) by about 13 times. The 1,25D3-evoked stimulation of HaCaT CAMP expression was associated with attenuated VDR mRNA and protein expression. Treatment with RXRα short interfering RNA reversed the 1,25D3-induced CAMP expression in HaCaT cells, showing that RXRα is involved in the up-regulation of CAMP by 1,25D3. We conclude that the 1,25D3-evoked stimulation of CAMP expression in human skin keratinocytes is dependent on RXRα but is not associated with the up-regulation of VDR expression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cathelicidin, Keratinocyte, Retinoid X receptor, Vitamin D, Vitamin D receptor
in
Cell and Tissue Research
pages
10 pages
publisher
Springer
external identifiers
  • Scopus:84976384416
  • WOS:000386611700009
ISSN
0302-766X
DOI
10.1007/s00441-016-2449-z
language
English
LU publication?
yes
id
f2cbde11-ae3d-4c52-a511-1b6fff309868
date added to LUP
2016-07-18 12:37:28
date last changed
2017-01-01 08:30:39
@article{f2cbde11-ae3d-4c52-a511-1b6fff309868,
  abstract     = {<p>The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin keratinocytes (HaCaT cells). Gene analysis revealed that human skin biopsies expressed higher levels of both CAMP and RXRα mRNA than human gingival biopsies, whereas VDR and RXRβ transcript levels were similar in skin and gingiva. In HaCaT cells, treatment with 1,25D3 (5 nM and 1 μM) for 4 and 24 h up-regulated CAMP mRNA several fold, and treatment with 1,25D3 for 24 h increased protein expression of the pro-form of LL-37 (hCAP-18) by about 13 times. The 1,25D3-evoked stimulation of HaCaT CAMP expression was associated with attenuated VDR mRNA and protein expression. Treatment with RXRα short interfering RNA reversed the 1,25D3-induced CAMP expression in HaCaT cells, showing that RXRα is involved in the up-regulation of CAMP by 1,25D3. We conclude that the 1,25D3-evoked stimulation of CAMP expression in human skin keratinocytes is dependent on RXRα but is not associated with the up-regulation of VDR expression.</p>},
  author       = {Svensson, Daniel and Nebel, Daniel and Voss, Ulrikke and Ekblad, Eva and Nilsson, Bengt Olof},
  issn         = {0302-766X},
  keyword      = {Cathelicidin,Keratinocyte,Retinoid X receptor,Vitamin D,Vitamin D receptor},
  language     = {eng},
  month        = {06},
  pages        = {1--10},
  publisher    = {Springer},
  series       = {Cell and Tissue Research},
  title        = {Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α},
  url          = {http://dx.doi.org/10.1007/s00441-016-2449-z},
  year         = {2016},
}