Combined Benefits of a PAR2 Inhibitor and Stratum Corneum Acidification for Murine Atopic Dermatitis  Takashi Sakai, Yutaka Hatano, Haruna Matsuda-Hirose,

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Combined Benefits of a PAR2 Inhibitor and Stratum Corneum Acidification for Murine Atopic Dermatitis  Takashi Sakai, Yutaka Hatano, Haruna Matsuda-Hirose, Wei Zhang, Daisuke Takahashi, Se Kyoo Jeong, Peter M. Elias, Sakuhei Fujiwara  Journal of Investigative Dermatology  Volume 136, Issue 2, Pages 538-541 (February 2016) DOI: 10.1016/j.jid.2015.11.011 Copyright © 2015 The Authors Terms and Conditions

Figure 1 Therapeutic effects of treatments with protease-activated receptor-2 (PAR2) antagonist and lactobionic acid (LBA). (a) Transepidermal water loss (TEWL) and (b) stratum corneum (SC) hydration in normal mice and oxazolone-induced atopic dermatitis-like dermatitis (Ox-AD) mice before and after topical application. (c) SC pH in normal mice and Ox-AD mice after topical application. (a) N = 8; (b) N = 16; (c) N = 12 in. AU, arbitrary units; NS, not significant. **P < 0.01; ***P < 0.001. LBA, lactobionic acid; Ox-AD, oxazolone-induced atopic-dermatitis-like dermatitis; PAR2, protease-activated receptor-2; SC, stratum corneum; TEWL, transepidermal water loss. Journal of Investigative Dermatology 2016 136, 538-541DOI: (10.1016/j.jid.2015.11.011) Copyright © 2015 The Authors Terms and Conditions

Figure 2 Effect of treatment with protease-activated receptor-2 (PAR2) antagonist and lactobionic acid (LBA) on activity of serine protease and β-glucocerebrosidase (β-GlcCer’ase) and expression of thymic stromal lymphopoietin (TSLP). (a) Serine protease activity and (b) β-GlcCer’ase activity in zymographic assessment and (c) TSLP expression in immunohistochemical analysis in oxazolone-induced atopic dermatitis-like dermatitis (Ox-AD) mice after topical application. (a) Green staining in SC and stratum granulosum area of the epidermis represents serine protease activity. (b) Red staining reveals β-GlcCer’ase activity. (c) Green staining reveals expression of TSLP. (d) Real-time PCR reveals that gene expression of TSLP from whole skin was reduced only with treatment by coapplication of PAR2 antagonist and LBA compared to vehicle group. N = 5–8. (e) Similar expression patterns of TSLP in epidermal sheets obtained by analysis of protein levels. N = 3. NS, not significant. *P < 0.05. Bar = 50 μm. β-GlcCer’ase, β-glucocerebrosidase; LBA, lactobionic acid; PAR2, protease-activated receptor-2; TSLP, thymic stromal lymphopoietin. Journal of Investigative Dermatology 2016 136, 538-541DOI: (10.1016/j.jid.2015.11.011) Copyright © 2015 The Authors Terms and Conditions