PH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion

被引:320
作者
Hachem, JP
Crumrine, D
Fluhr, J
Brown, BE
Feingold, KR
Elias, PM
机构
[1] Vet Affairs Med Ctr, Dermatol Sect, Dermatol Serv 190, San Francisco, CA 94121 USA
[2] Univ Calif San Francisco, Med Ctr, Dept Dermatol, San Francisco, CA 94143 USA
[3] Vet Affairs Med Ctr, Metab Sect, San Francisco, CA 94121 USA
[4] Univ Jena, Dept Dermatol, D-6900 Jena, Germany
关键词
corneodesmosome; permeability barrier function; serine protease; serine protease inhibitor; stratum corneum; superbase; transepidermal water loss;
D O I
10.1046/j.1523-1747.2003.12365.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Both exposure of stratum corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and stratum corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of stratum corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and stratum corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and stratum corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized stratum corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that stratum corneum neutralization alone provokes stratum corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased stratum corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.
引用
收藏
页码:345 / 353
页数:9
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