title: Zinc gluconate is an agonist of peroxisome proliferator-activated receptor-α in the epidermis.
abstract: Peroxisome proliferator-activated receptors-α (PPARs-α) 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-α 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-α protein expression using immunohistochemistry, PPAR-α DNA-binding activity using an ELISA-like technique, and PPAR-α mRNA levels using quantitative PCR. On the one hand, we found that PPAR-α epidermal protein expression was stimulated by LPS and that LPS suppressed PPAR-α mRNA expression, without modifying its function. On the other hand, in inflammatory LPS-stimulated explants, zinc gluconate significantly upregulated PPAR-α function and mRNA expression level, without changing its epidermal protein expression. These results suggest that zinc gluconate may be a PPAR-α agonist, which might play a role in the anti-inflammatory activity of this molecule.
authors.affiliation: INSERM U892, Nantes University Hospital, Nantes, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Poiraud
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Quereux
authors.forename: Anne-Chantal
authors.initials: AC
authors.lastname: Knol
authors.forename: Rémy
authors.initials: R
authors.lastname: Allix
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism*; D005942:Gluconates / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005942:Gluconates; D008070:Lipopolysaccharides; D047493:PPAR alpha; D012333:RNA, Messenger; C030691:gluconic acid