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Estrogen inhibits acute and chronic contact hypersensitivity response in mice
Abstracts / Journal of Dermatological Science 84 (2016) e1–e88
P11-26 Estrogen inhibits acute and chronic contact hypersensitivity response in mice Chen Yue 1,2,∗ , Hiroo Yokozeki 2 , Kazumoto Katagiri 1 1
Department of Dermatology, Dokkyo Medical University Koshigaya Hospital, Saita, Japan 2 Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan Background: Cyclical variation of progesterone and estrogen in menstrual cycle influences many skin condition such as atopic dermatitis. Recently we found estrogen replace treatment restored impaired permeability barrier function in ovariectomized mice. However it is not clear whether estrogen relieves atopic dermatitis. Purpose: This study is designated to elucidate the effects of estrogen on acute and chronic contact hypersensitivity (CHS) response in mice as a model of atopic dermatitis. Materials and methods: Acute and chronic CHS induced by TNCB was evaluated using ovariectomized Balb/c mice with or without 17 beta-estradiol (E2) replacement treatment. Mice were given ovariectomy and a E2 controlled-release pellet subcutaneously 1 wk before sensitization, and were challenged with TNCB 1 wk later as day 0, and were then repeatedly challenged every other day until day 24. Results and discussion: E2 suppressed irritant dermatitis induced by TNCB at sensitization. E2 also inhibited acute CHS response on day 0, but CHS response within 24 h after TNCB treatment at day 4, 8 and 16 in mice with E2 were comparable with those of mice without E2. Chronic CHS responses, which were evaluated 24 h after TNCB challenge ever other day until day 24, was also inhibited by E2. These results suggest that full development of CHS delayed in E2-treated mice, probably due to attenuation of irritation or other. Inhibitory effect of E2 on chronic CHS might be caused not by impairment of immune function but other factor such as epidermal barrier and dermal components that are most important target of E2 in the skin. This study showed the possibility of estrogen as a new therapeutic approach for atopic dermatitis. http://dx.doi.org/10.1016/j.jdermsci.2016.08.236 Category 12(P12): Photobiology P12-01[II-7] Establishment and characterization of iPS cells derived from XPA patients Chihiro Shimizuhira 1,∗ , Hidaka Yokota 1,2 , Shinichi Moriwaki 3 , Yoshinori Yoshida 2 , Yoshiki Miyachi 1 , Shinya Yamanaka 2 , Kenji Kabashima 1 1 Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 2 Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Japan 3 Department of Dermatology, Osaka Medical College, Japan
Xeroderma pigmentosum group A (XPA) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. Currently, more investigation is needed to clarify the pathogenesis of XPA, such as how neurological
e77
abnormality is induced. Recently, patient-specific induced pluripotent stem cells (iPS cells) have been introduced to study its underlying mechanisms. In this study, we generated iPS cells from dermal fibroblasts of XPA patients (XPA iPS cells) by reprogramming with episomal vectors. We confirmed that the XPA iPS cells expressed the human embryonic stem cell markers. Initially, we compared colony-forming ability of XPA iPS cells to analyze UV sensitivity. The colony counts of XPA iPS cells were decreased than control cells after UV irradiation. In addition, UV irradiation promote apoptotic XPA iPS cells. These findings suggest that high sensitivity to UV in XPA skin fibroblasts were reproduced even in iPS cells. Consistently, high UV sensitivity of XPA iPS cells was compensated by overexpressing XPA protein to XPA iPS cells. These results indicate that overexpression of XPA protein overcomes impaired DNA repair after UV irradiation in XPA. Then we applied the serum-free embryoid body-like culture to induce neural cells using iPSCs derived from patients and observed polysialylated isoforms of neural cell adhesion molecule expression. These findings suggest that XPA iPS cells may provide a useful tool for elucidating the pathogenesis of XPA, especially for neurodegeneration, and for the development of iPS cell-based therapies for XPA. http://dx.doi.org/10.1016/j.jdermsci.2016.08.237 P12-02[C06-02] Irradiation by excimer lamp induces intraepidermal nerve degeneration and inhibits itch-related behavior in a dry-skin mouse model Atsuko Kamo 1,2,∗ , Mitsutoshi Tominaga 1 , Yayoi Kamata 1 , Kazuyuki Kaneda 3 , Kyi C. Ko 1 , Hironori Matsuda 1 , Utako Kimura 4 , Kenji Takamori 4 1
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Japan 2 Department of Nursing, School of Health Sciences, Tokai University, Japan 3 Ushio Inc., Japan 4 Department of Dermatology, Juntendo University Urayasu Hospital, Japan Epidermal hyperinnervation is considered a factor underlying intractable pruritus associated with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. We previously reported that excimer lamp irradiation shows an antihyperinnervative effect in non-pruritic dry skin model mice, though no change in epidermal expression of axonal guidance molecules was observed. Here we investigated the antipruritic effects of excimer lamp irradiation and its mechanism using three systems. A single irradiation session by excimer lamp significantly inhibited scratch behavior in AD model mice, facilitating improvement in dermatitis score. In cultured dorsal root ganglion cells, irradiation by excimer lamp increased bleb formation in nerve fibers, a morphological marker of nerve degeneration, and decreased the expression of nicotinamide mononucleotide adenylyltransferase 2, a neuronal survival factor. Using a cut-off filter (COF) with the excimer lamp, which blocks unwanted wavelength below 297 nm and decreases cyclobutane pyrimidine dimer (CPD) production which is a marker of DNA damage, we assessed the antihyperinnervative effect and CPD production in the same dry-skin model mouse. Irradiation by excimer lamp with COF decreased CPD production in epidermal keratinocytes of the dry-skin model, while maintaining the antihyperinnervative effect. Thus, excimer lamp irradiation with a COF
P11-26 Estrogen inhibits acute and chronic contact hypersensitivity response in mice Chen Yue 1,2,∗ , Hiroo Yokozeki 2 , Kazumoto Katagiri 1 1
Department of Dermatology, Dokkyo Medical University Koshigaya Hospital, Saita, Japan 2 Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan Background: Cyclical variation of progesterone and estrogen in menstrual cycle influences many skin condition such as atopic dermatitis. Recently we found estrogen replace treatment restored impaired permeability barrier function in ovariectomized mice. However it is not clear whether estrogen relieves atopic dermatitis. Purpose: This study is designated to elucidate the effects of estrogen on acute and chronic contact hypersensitivity (CHS) response in mice as a model of atopic dermatitis. Materials and methods: Acute and chronic CHS induced by TNCB was evaluated using ovariectomized Balb/c mice with or without 17 beta-estradiol (E2) replacement treatment. Mice were given ovariectomy and a E2 controlled-release pellet subcutaneously 1 wk before sensitization, and were challenged with TNCB 1 wk later as day 0, and were then repeatedly challenged every other day until day 24. Results and discussion: E2 suppressed irritant dermatitis induced by TNCB at sensitization. E2 also inhibited acute CHS response on day 0, but CHS response within 24 h after TNCB treatment at day 4, 8 and 16 in mice with E2 were comparable with those of mice without E2. Chronic CHS responses, which were evaluated 24 h after TNCB challenge ever other day until day 24, was also inhibited by E2. These results suggest that full development of CHS delayed in E2-treated mice, probably due to attenuation of irritation or other. Inhibitory effect of E2 on chronic CHS might be caused not by impairment of immune function but other factor such as epidermal barrier and dermal components that are most important target of E2 in the skin. This study showed the possibility of estrogen as a new therapeutic approach for atopic dermatitis. http://dx.doi.org/10.1016/j.jdermsci.2016.08.236 Category 12(P12): Photobiology P12-01[II-7] Establishment and characterization of iPS cells derived from XPA patients Chihiro Shimizuhira 1,∗ , Hidaka Yokota 1,2 , Shinichi Moriwaki 3 , Yoshinori Yoshida 2 , Yoshiki Miyachi 1 , Shinya Yamanaka 2 , Kenji Kabashima 1 1 Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 2 Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Japan 3 Department of Dermatology, Osaka Medical College, Japan
Xeroderma pigmentosum group A (XPA) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. Currently, more investigation is needed to clarify the pathogenesis of XPA, such as how neurological
e77
abnormality is induced. Recently, patient-specific induced pluripotent stem cells (iPS cells) have been introduced to study its underlying mechanisms. In this study, we generated iPS cells from dermal fibroblasts of XPA patients (XPA iPS cells) by reprogramming with episomal vectors. We confirmed that the XPA iPS cells expressed the human embryonic stem cell markers. Initially, we compared colony-forming ability of XPA iPS cells to analyze UV sensitivity. The colony counts of XPA iPS cells were decreased than control cells after UV irradiation. In addition, UV irradiation promote apoptotic XPA iPS cells. These findings suggest that high sensitivity to UV in XPA skin fibroblasts were reproduced even in iPS cells. Consistently, high UV sensitivity of XPA iPS cells was compensated by overexpressing XPA protein to XPA iPS cells. These results indicate that overexpression of XPA protein overcomes impaired DNA repair after UV irradiation in XPA. Then we applied the serum-free embryoid body-like culture to induce neural cells using iPSCs derived from patients and observed polysialylated isoforms of neural cell adhesion molecule expression. These findings suggest that XPA iPS cells may provide a useful tool for elucidating the pathogenesis of XPA, especially for neurodegeneration, and for the development of iPS cell-based therapies for XPA. http://dx.doi.org/10.1016/j.jdermsci.2016.08.237 P12-02[C06-02] Irradiation by excimer lamp induces intraepidermal nerve degeneration and inhibits itch-related behavior in a dry-skin mouse model Atsuko Kamo 1,2,∗ , Mitsutoshi Tominaga 1 , Yayoi Kamata 1 , Kazuyuki Kaneda 3 , Kyi C. Ko 1 , Hironori Matsuda 1 , Utako Kimura 4 , Kenji Takamori 4 1
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Japan 2 Department of Nursing, School of Health Sciences, Tokai University, Japan 3 Ushio Inc., Japan 4 Department of Dermatology, Juntendo University Urayasu Hospital, Japan Epidermal hyperinnervation is considered a factor underlying intractable pruritus associated with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. We previously reported that excimer lamp irradiation shows an antihyperinnervative effect in non-pruritic dry skin model mice, though no change in epidermal expression of axonal guidance molecules was observed. Here we investigated the antipruritic effects of excimer lamp irradiation and its mechanism using three systems. A single irradiation session by excimer lamp significantly inhibited scratch behavior in AD model mice, facilitating improvement in dermatitis score. In cultured dorsal root ganglion cells, irradiation by excimer lamp increased bleb formation in nerve fibers, a morphological marker of nerve degeneration, and decreased the expression of nicotinamide mononucleotide adenylyltransferase 2, a neuronal survival factor. Using a cut-off filter (COF) with the excimer lamp, which blocks unwanted wavelength below 297 nm and decreases cyclobutane pyrimidine dimer (CPD) production which is a marker of DNA damage, we assessed the antihyperinnervative effect and CPD production in the same dry-skin model mouse. Irradiation by excimer lamp with COF decreased CPD production in epidermal keratinocytes of the dry-skin model, while maintaining the antihyperinnervative effect. Thus, excimer lamp irradiation with a COF