A novel treatment for skin repair using a combination of spironolactone and vitamin D3

Dauren Biyashev, Ummiye V. Onay, Prarthana Dalal, Michael Demczuk, Spencer Evans, José Marc Techner, Kurt Q. Lu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)170-182
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1480
Issue number1
DOIs
StatePublished - Nov 17 2020

Keywords

  • nitrogen mustard
  • skin injury
  • spironolactone
  • vitamin D

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Fingerprint

Dive into the research topics of 'A novel treatment for skin repair using a combination of spironolactone and vitamin D3'. Together they form a unique fingerprint.

Cite this