A novel treatment for skin repair using a combination of spironolactone and vitamin D3.
Dauren BiyashevUmmiye V OnayPrarthana DalalMichael DemczukSpencer EvansJosé-Marc TechnerKurt Q LuPublished in: Annals of the New York Academy of Sciences (2020)
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.
Keyphrases
- wound healing
- immune response
- oxidative stress
- nuclear factor
- photodynamic therapy
- poor prognosis
- machine learning
- type diabetes
- inflammatory response
- cell proliferation
- early onset
- cell death
- nitric oxide
- soft tissue
- adipose tissue
- long non coding rna
- signaling pathway
- insulin resistance
- smoking cessation
- electronic health record