Defective maintenance of pH of stratum corneum is correlated with preferential emergence and exacerbation of atopic-dermatitis-like dermatitis in flaky-tail mice

BackgroundNeutralization 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.ObjectiveWe examined possible correlations between disturbance of responses to an exogenous stimulus of SC neutralization and the preferential emergence of AD-like dermatitis in FTM.MethodsFTM 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.ResultsThe 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.ConclusionOur results suggest that defective maintenance of pH of SC is correlated with emergence and exacerbation of AD-like dermatitis in FTM.