1. ¹Dermatology and Medical Service, Veterans Affairs Medical Center, San Francisco, California, USA
2. ²Bioskin, Berlin, Germany
3. ³Department of Dermatology, University of California, San Francisco, California, USA
4. ⁴Department of Medicine, University of California, San Francisco, California, USA

Correspondence: Dr Joachim W. Fluhr, Dermatology and Medical Service (190), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121, USA. E-mail: joachim.fluhr@gmx.Net

Received 24 May 2007; Revised 29 April 2008; Accepted 30 April 2008; Published online 14 August 2008.

Abstract

Previous studies have shown that pH declines from between 6 and 7 at birth to adult levels (pH 5.0–5.5) over 5–6 days in neonatal rat stratum corneum (SC). As a result, at birth, neonatal epidermis displays decreased permeability barrier homeostasis and SC integrity, improving days 5–6. We determined here whether peroxisome proliferator-activated receptor (PPAR) activators accelerate postnatal SC acidification. Topical treatment with two different PPAR activators, clofibrate and WY14643, accelerated the postnatal decline in SC surface pH, whereas treatment with PPAR activators did not and a PPAR/ activator had only a modest effect. Treatment with clofibrate significantly accelerated normalization of barrier function. The morphological basis for the improvement in barrier function in PPAR-treated animals includes accelerated secretion of lamellar bodies and enhanced, postsecretory processing of secreted lamellar body contents into mature lamellar membranes. Activity of -glucocerebrosidase increased after PPAR-activator treatment. PPAR activator also improved SC integrity, which correlated with an increase in corneodesmosome density and increased desmoglein-1 content, with a decline in serine protease activity. Topical treatment of newborn animals with a PPAR activator increased secretory phospholipase A2 activity, which likely accounts for accelerated SC acidification. Thus, PPAR activators accelerate neonatal SC acidification, in parallel with improved permeability homeostasis and SC integrity/cohesion. Hence, PPAR activators might be useful to prevent or treat certain common neonatal dermatoses.