Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially.

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Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially Inhibited by Acidification Hae-Jin Lee, Noo Ri Lee, Minyoung Jung, Dong Hye Kim, Eung Ho Choi Journal of Investigative Dermatology Volume 135, Issue 12, Pages 3025-3033 (December 2015) DOI: 10.1038/jid.2015.333 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Repeated epicutaneous application of HDM (Dp) extract followed by nasal inhalation provokes remarkable AD-like lesions and barrier disruption in NC/Nga mice. Symptoms were aggravated by neutral cream, but neither aggravated nor improved by acidic cream. Systemic allergic inflammation was aggravated by neutral cream but partially improved by acidic cream. (a) Time course of skin surface pH after application of acidic or neutral cream (n=4, each group). (b) Eczema scores and gross appearance, (c) basal TEWL, (d) SC hydration, (e) skin surface pH, (f) serum IgE, and (g) TSLP after Dp treatment were compared among treatment groups. ANOVA showed P<0.05 in all measurements except (e) surface pH. Results are mean±SEM. *P<0.05, compared with control (BALB/c SLS+Dp); +P<0.05, compared with NC/Nga SLS+Dp. (n=6, each group). ANOVA, analysis of variance; SC, stratum corneum; TEWL, transepidermal water loss. Journal of Investigative Dermatology 2015 135, 3025-3033DOI: (10.1038/jid.2015.333) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Cutaneous allergic inflammation and abnormal epidermal differentiation induced in NC/Nga mice are aggravated by neutral cream but partially improved by acidic cream. (a) Tissue eosinophils were counted with H&E staining, and (b) expression of epidermal differentiation markers (filaggrin, involucrin, loricrin), PAR-2, and TSLP were measured by immunohistochemical staining in skin specimens taken after repeated epicutaneous treatment and nasal inhalation of Dp. (a) ANOVA and (b) Kruskal–Wallis test showed P<0.05 in all measurements. Results are mean±SEM. *P<0.05, compared with control (BALB/c SLS+Dp); +P<0.05, compared with NC/Nga SLS+Dp. (n=6, each group). ANOVA, analysis of variance; SLS, sodium lauryl sulfate; TSLP, thymic stromal lymphopoietin. Journal of Investigative Dermatology 2015 135, 3025-3033DOI: (10.1038/jid.2015.333) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Repeated epicutaneous application of house dust mite (Dp) extract followed by nasal inhalation produces asthma-like inflammatory response as well as AD lesions in NC/Nga mice, implying atopic march. Symptoms are aggravated by neutral cream, but partially improved by acidic cream. BAL, real time quantitative–PCR for mRNA expression, and immunohistochemical staining of PAR-2 and TSLP were performed in the lung tissue after Dp treatment. (a) Total cells and (b) individual cell count in the BAL, and (c and d) mRNA and (e) expression of PAR-2 and TSLP in the lung tissue were measured. (a–d) ANOVA and (e) Kruskal–Wallis test showed P<0.05 in all measurements. Results are mean±SEM. *P<0.05, compared with control (BALB/c SLS+Dp); +P<0.05, compared with NC/Nga SLS+Dp and NC/Nga SLS+Dp+pH 2.8. (n=6, each group). ANOVA, analysis of variance; BAL, bronchoalveolar lavage; SLS, sodium lauryl sulfate; TSLP, thymic stromal lymphopoietin. Journal of Investigative Dermatology 2015 135, 3025-3033DOI: (10.1038/jid.2015.333) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Establishment of a model of atopic march in NC/Nga mice by epicutaneous application and subsequent nasal inhalation of house dust mite, and the intervention by topical acidic or neutral cream. Journal of Investigative Dermatology 2015 135, 3025-3033DOI: (10.1038/jid.2015.333) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions