Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis.
Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans.
Hatano
Yutaka
Y
Dermatology Service, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Man
Mao-Qiang
MQ
Uchida
Yoshikazu
Y
Crumrine
Debra
D
Scharschmidt
Tiffany C
TC
Kim
Esther G
EG
Mauro
Theodora M
TM
Feingold
Kenneth R
KR
Elias
Peter M
PM
Holleran
Walter M
WM
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000473:pathology / Q000517:prevention & control; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D004187:Disaccharides / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006241:Haptens / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D007073:Immunoglobulin E / Q000097:blood; D008051:Lipid Bilayers / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D010081:Oxazolone / Q000633:toxicity; D012697:Serine Endopeptidases / Q000378:metabolism; D018418:Th2 Cells / Q000473:pathology
D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; D004187:Disaccharides; D006241:Haptens; D008051:Lipid Bilayers; D010081:Oxazolone; D007073:Immunoglobulin E; C005608:lactobionic acid; D012697:Serine Endopeptidases