pH Directly Regulates Epidermal Permeability Barrier Homeostasis, and Stratum Corneum Integrity/Cohesion

To establish de¢nitively the apparent link between stratum corneum pH and barrier homeostasis and SC integrity/cohesion, we developed a new model in which SC pH could be modulated directly, utilizing topical applications of low concentrations of two ‘‘superbases’’, 1,1,3,3 -tetramethyl-guanidine and 1,8-diazabicyclo undec-7ene, to raise and sustain pH to speci¢c levels within the SC, without evidence of toxicity at the low concentrations employed

Jean-Pierre Hachem

2003

Scholarcy highlights

  • Both exposure of stratum corneum to neutral pH buffers and blockade of acidi¢cation mechanisms disturb cutaneous permeability barrier homeostasis and stratum corneum integrity/cohesion, but these approaches all introduce potentially confounding variables
  • To establish de¢nitively the apparent link between stratum corneum pH and barrier homeostasis and SC integrity/cohesion, we developed a new model in which SC pH could be modulated directly, utilizing topical applications of low concentrations of two ‘‘superbases’’, 1,1,3,3 -tetramethyl-guanidine and 1,8-diazabicyclo undec-7ene, to raise and sustain pH to speci¢c levels within the SC, without evidence of toxicity at the low concentrations employed
  • Ethanol, and HCl were from Fisher Scienti¢c, whereas TMG, DBU, phenylmethylsulfonyl £uoride, chymostatin, soybean trypsin inhibitor, and aprotinin were from Sigma Chemical
  • Despite the sustained elevation in SC pH, both basal transepidermal water loss and SC hydration levels remained unchanged in superbase-treated sites
  • Using two unrelated superbases that raise pH selectively within the SC without evidence of toxicity or in£ammation, we demonstrated that both cutaneous permeability barrier homeostasis and SC integrity and cohesion are perturbed when SC pH is elevated
  • The use of superbases, as employed here, to raise SC pH directly avoids the potential pitfalls of other methods to elevate pH experimentally, as used by our and other laboratories
  • Our studies have elucidated two such pathways, it is very likely that the activity of other proteins/enzymes in the stratum corneum will be altered by increases in SC pH, and that such increases will initiate other, as yet unde¢ned, functional abnormalities either in the SC or within deeper skin layers

Need more features? Save interactive summary cards to your Scholarcy Library.