Zinc gluconate is an agonist of peroxisome proliferator-activated receptor-a in the epidermis

Peroxisome proliferator-activated receptors-a (PPARs-a) are nuclear receptors with anti-inflammatory properties. Zinc gluconate is efficient in the treatment of several inflammatory dermatoses. The aim of our work was to determine whether the modulation of PPAR-a expression and activity could be one of the mechanisms of action of zinc gluconate anti-inflammatory activity in inflammatory dermatoses. Thus, we used ex vivo skin explants incubated with lipopolysaccharide (LPS), a pro-inflammatory molecule, with or without zinc gluconate. We evaluated PPAR-a protein expression using immunohistochemistry, PPAR-a DNA-binding activity using an ELISA-like technique, and PPAR-a mRNA levels using quantitative PCR. On the one hand, we found that PPAR-a epidermal protein expression was stimulated by LPS and that LPS suppressed PPAR-a mRNA expression, without modifying its function. On the other hand, in inflammatory LPS-stimulated explants, zinc gluconate significantly upregulated PPAR-a function and mRNA expression level, without changing its epidermal protein expression. These results suggest that zinc gluconate may be a PPAR-a agonist, which might play a role in the anti-inflammatory activity of this molecule.