A novel treatment for skin repair using a combination of spironolactone and vitamin D3.
Animals
Apoptosis
/ drug effects
Cholecalciferol
/ pharmacology
Female
Gene Expression Regulation
/ drug effects
Macrophages
/ metabolism
Mechlorethamine
/ toxicity
Mice
RAW 264.7 Cells
Skin
/ injuries
Spironolactone
/ pharmacology
Wound Healing
/ drug effects
Wounds and Injuries
/ chemically induced
nitrogen mustard
skin injury
spironolactone
vitamin D
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
15
04
2020
revised:
10
07
2020
accepted:
13
08
2020
pubmed:
7
9
2020
medline:
31
12
2020
entrez:
6
9
2020
Statut:
ppublish
Résumé
Injury of the skin from exposure to toxic chemicals leads to the release of inflammatory mediators and the recruitment of immune cells. Nitrogen mustard (NM) and other alkylating agents cause severe cutaneous damage for which there are limited treatment options. Here, we show that combined treatment of vitamin D3 (VD3) and spironolactone (SP), a mineralocorticoid receptor antagonist, significantly improves the resolution of inflammation and accelerates wound healing after NM exposure. SP enhanced the inhibitory effect of VD3 on nuclear factor-kB activity. Combined treatment of NM-exposed mice with VD3 and SP synergistically inhibited the expression of iNOS in the skin and decreased the expression of matrix metallopeptidase-9, C-C motif chemokine ligand 2, interleukin (IL)-1α, and IL-1β. The combined treatment decreased the number of local proinflammatory M1 macrophages resulting in an increase in the M2/M1 ratio in the wound microenvironment. Apoptosis was also decreased in the skin after combined treatment. Together, this creates a proresolution state, resulting in more rapid wound closure. Combined VD3 and SP treatment is effective in modulating the immune response and activating anti-inflammatory pathways in macrophages to facilitate tissue repair. Altogether, these data demonstrate that VD3 and SP may constitute an effective treatment regimen to improve wound healing after NM or other skin chemical injury.
Identifiants
pubmed: 32892377
doi: 10.1111/nyas.14485
pmc: PMC7754145
doi:
Substances chimiques
Cholecalciferol
1C6V77QF41
Spironolactone
27O7W4T232
Mechlorethamine
50D9XSG0VR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-182Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR057216
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Organisme : NIAMS NIH HHS
ID : U01 AR064144
Pays : United States
Organisme : NIAMS NIH HHS
ID : U01 AR071168
Pays : United States
Informations de copyright
© 2020 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.
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