title: Defective maintenance of pH of stratum corneum is correlated with preferential emergence and exacerbation of atopic-dermatitis-like dermatitis in flaky-tail mice.
abstract: BACKGROUND
  Neutralization of stratum corneum (SC) pH, which is induced by a variety of stimuli, such as scratching, use of soap and inflammation, can stimulate activity of serine protease (SPase). Activation of SPase induces production of thymic stromal lymphopoietin (TSLP) through protease-activated receptor-2. Both reduced expression of natural moisturizing factors, which are required for maintenance of SC pH, and the preferential development of atopic dermatitis (AD)-like dermatitis are found in flaky-tail mice (FTM) with a loss-of-function mutation in filaggrin.
  
  
  OBJECTIVE
  We examined possible correlations between disturbance of responses to an exogenous stimulus of SC neutralization and the preferential emergence of AD-like dermatitis in FTM.
  
  
  METHODS
  FTM and wild-type mice (C57BL/6) were subjected to an SC-neutralization stimulus via application of 1,1,3,3-tetramethylguanidine (TMG). TMG was applied to young mice at a time when FTM had not yet developed significant dermatitis, and we examined their ability to maintain SC acidity and several parameters associated with AD-like dermatitis.
  
  
  RESULTS
  The recovery of SC pH after the application of TMG was delayed in FTM, presumably because of unchanged expression of Na(+)/H(+) antiporter 1, which is involved in maintenance of SC acidity. Cutaneous inflammation with elevated SPase activity and serum levels of TSLP, thymus and activation-regulated chemokine and IgE were induced only in TMG-treated FTM.
  
  
  CONCLUSIONS
  Our results suggest that defective maintenance of pH of SC is correlated with emergence and exacerbation of AD-like dermatitis in FTM.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan. Electronic address: hatano@oita-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D054414:Chemokine CCL17 / Q000097:blood; D016207:Cytokines / Q000097:blood; D003876:Dermatitis, Atopic / Q000209:etiology*; D004817:Epidermis / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006146:Guanidines; D006863:Hydrogen-Ion Concentration; D007073:Immunoglobulin E / Q000097:blood; D008810:Mice, Inbred C57BL; D057057:Serine Proteases / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D027682:Cation Transport Proteins; D054414:Chemokine CCL17; D016207:Cytokines; D006146:Guanidines; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D007073:Immunoglobulin E; D057057:Serine Proteases; C477069:1,1,3,3-tetramethylguanidine; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: Atopic dermatitis; Filaggrin; Flaky-tail mice; Stratum corneum pH