Murine atopic dermatitis responds to peroxisome proliferator-activated receptors alpha and beta/delta (but not gamma) and liver X receptor activators

J Allergy Clin Immunol. 2010 Jan;125(1):160-9.e1-5. doi: 10.1016/j.jaci.2009.06.049. Epub 2009 Oct 8.


Background: Atopic dermatitis (AD) is a chronic inflammatory dermatosis now increasingly linked to mutations that alter the structure and function of the stratum corneum. Activators of peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma and liver X receptor (LXR) regulate epidermal protein and lipid production, leading to superior barrier function. Additionally, some of these activators exhibit potent antihyperplastic and anti-inflammatory activity in irritant contact dermatitis and acute allergic contact dermatitis murine models.

Objective: We evaluated the efficacy of PPAR/LXR activation in a hapten (oxazolone [Ox])-induced AD-like model (Ox-AD) in hairless mice.

Methods: Ox-AD was established with 10 Ox challenges (every other day) on the flank. After the establishment of Ox-AD, twice-daily topical application with individual PPAR/LXR activators was then performed for 4 days, with continued Ox challenges every other day. The efficacy of topical PPAR/LXR activators to reduce parameters of Ox-AD was assessed physiologically, morphologically, and immunologically.

Results: Certain topical activators of PPARalpha, PPARbeta/delta, and LXR, but not activators of PPARgamma, reversed the clinical dermatosis, significantly improved barrier function, and increased stratum corneum hydration in Ox-AD mice. In addition, the same activators, but again not PPARgamma, largely reversed the immunologic abnormalities in Ox-AD mice, including the increased T(H)2 markers, such as tissue eosinophil/mast cell density, serum thymus and activation-related chemokine levels, the density of chemoattractant receptor-homologous molecule expressed on T(H)2-positive lymphocytes (but not serum IgE levels), and reduced IL-1alpha and TNF-alpha activation, despite ongoing hapten challenges.

Conclusion: These results suggest that topical applications of certain activators/ligands of PPARalpha, PPARbeta/delta, and LXR could be useful for the treatment of AD in human subjects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Topical
  • Animals
  • Cytokines / metabolism
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Epidermis / immunology
  • Epidermis / pathology
  • Female
  • Humans
  • Liver X Receptors
  • Mice
  • Mice, Hairless
  • Orphan Nuclear Receptors / agonists*
  • Oxazolone / administration & dosage
  • PPAR alpha / agonists*
  • PPAR delta / agonists*
  • PPAR-beta / agonists*
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Th2 Cells / immunology
  • Treatment Outcome


  • Cytokines
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • PPAR alpha
  • PPAR delta
  • PPAR-beta
  • Peroxisome Proliferator-Activated Receptors
  • Oxazolone