Takashi Sakai1, Yutaka Hatano2, Wei Zhang1, Sakuhei Fujiwara1. 1. Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan. 2. Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan. Electronic address: hatano@oita-u.ac.jp.
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. CONCLUSION: Our results suggest that defective maintenance of pH of SC is correlated with emergence and exacerbation of AD-like dermatitis in FTM.
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. CONCLUSION: Our results suggest that defective maintenance of pH of SC is correlated with emergence and exacerbation of AD-like dermatitis in FTM.
Authors: Jung Eun Kim; Hyun Jeong Kim; Bark-Lynn Lew; Kyung Ho Lee; Seung Phil Hong; Yong Hyun Jang; Kui Young Park; Seong Jun Seo; Jung Min Bae; Eung Ho Choi; Ki Beom Suhr; Seung Chul Lee; Hyun Chang Ko; Young Lip Park; Sang Wook Son; Young Jun Seo; Yang Won Lee; Sang Hyun Cho; Chun Wook Park; Joo Young Roh Journal: Ann Dermatol Date: 2015-10-02 Impact factor: 1.444