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Intense pulsed light increases hyaluronan and CD44 in the epidermal keratinocytes and improves age-related epidermal structure defects
Abstracts / Journal of Dermatological Science 84 (2016) e89–e180
Conclusions: Using SRS microscopy, the differentiation status of epidermal keratinocytes was distinguished together with the distribution pattern of chemical components. http://dx.doi.org/10.1016/j.jdermsci.2016.08.402 P05-21[O1-09] Intense pulsed light increases hyaluronan and CD44 in the epidermal keratinocytes and improves age-related epidermal structure defects Sang Eun Lee 1,∗ , Hye Rang On 1 , Hee Jung Lee 2 1 Department of Dermatology, Yonsei University College of Medicine, Seoul, South Korea 2 Department of Dermatology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
Epidermal hyaluronan (HA) and its receptor CD44 regulate permeability barrier homeostasis and skin aging. Recently, agedependent change in the metabolism of HA is suggested be responsible for these epidermal dysfunctions. Intense pulsed light (IPL) has been reported to be effective for improving photoaged skin. However, little is known about the effects of IPL on epidermal HA metabolism. We investigated whether IPL treatment can induce HA and CD44 expression in keratinocytes, which in turn contributes to improvement of age-related epidermal dysfunctions. The dorsal skin of 8 week-old (young) hairless mice and 47 week-old (aged) C57BL/6J mice was irradiated by IPL (570 nm cut-off filter, pulse interval of 20 ms, fluence 13 J/cm2 ). Before treatment and from 1–7 days after IPL treatment, the irradiated skin and unexposed skin specimens were examined. HA concentration assessed by ELISA and the mRNA levels of HABP4, CD44, and hyaluronan synthase (HAS) 3 were significantly upregulated in the epidermis of both young and old aged mice after IPL treatment, with the largest increase on day 1–3 and remained high for at least 7 days. In addition, IPL irradiation significantly increased HA content in culture supernatant of human keratinocytes and increased HAS3 and CD44 gene expression at 24–48 h after irradiation. IPL treatment also increases PCNA and filaggrin expression only in the aged mice epidermis. We demonstrated that IPL treatment increases HA and CD44 expression in epidermis and improves age-related epidermal dysfunction. These data suggest a new mechanism involved in the skin rejuvenation effect of IPL. Further studies are required to clarify the exact mechanism underlying the effect of IPL irradiation on epidermal HA metabolism. http://dx.doi.org/10.1016/j.jdermsci.2016.08.403 P05-22[O1-10] Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis Makiko Kido-Nakahara 1,∗ , Khudishta M. Aktar 1 , Masutaka Furue 1,2 , Takeshi Nakahara 2 1
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2 Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Endothelin 1 (ET-1) has been reported to evoke histamineindependent pruritus inmammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin
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inflammation of AD. To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and AD patients, and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line. We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and AD patients. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by either ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by either an endothelin A receptor antagonist, ERK1/2, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor. These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis in AD, which may be a future target for anti-pruritic agents. http://dx.doi.org/10.1016/j.jdermsci.2016.08.404 P05-23[O1-11] Regulatory roles of Syk in epidermal keratinocyte differentiation Nan-Lin Wu 1,2,∗ , Duen-Yi Huang 3 , Wan-Wan Lin 3 1
Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan 2 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 3 Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, is well recognized as a crucial regulator in the proximal signaling of diverse innate and adaptive immunoreceptors. More and more studies have demonstrated its expression in various cell types and also revealed its pleiotropic biologic functions in different immunological or malignant diseases. Drug design via targeting Syk is under development and has been applied in clinical trials. Epidermal keratinocytes of skin continuously undergo terminal differentiation, and such process is actually associated with defensive immunity. The expression of Syk in skin can be detected but the known functions of Syk in skin are still limited. Herein, we tried to explore the regulatory roles of Syk in keratinocyte differentiation by using primary human epidermal keratinocytes as the cell model and investigating the human specimens as well. In immunohistochemical studies, we found expression of Syk and phosphorylated Syk could be detected in normal skin tissue but the expression levels were reduced in the uppermost part of epidermis. In differentiating keratinocytes induced by phorbol 12-myristate 13-acetate and cell confluence, the expression of Syk and phosphorylated Syk were also suppressed. After treatment of Syk inhibitors or knocking down Syk in keratinocytes, the induction of mRNA and protein of various differentiation markers by cell confluence could be further enhanced. This study disclosed the in vivo expression pattern of Syk in skin and also unraveled the regulatory role of Syk in epidermal keratinocyte differentiation. These findings not only extend the current understanding of Syk in skin but also reveal the potential effects of Syk inhibitors in the treatment of skin diseases. http://dx.doi.org/10.1016/j.jdermsci.2016.08.405
Conclusions: Using SRS microscopy, the differentiation status of epidermal keratinocytes was distinguished together with the distribution pattern of chemical components. http://dx.doi.org/10.1016/j.jdermsci.2016.08.402 P05-21[O1-09] Intense pulsed light increases hyaluronan and CD44 in the epidermal keratinocytes and improves age-related epidermal structure defects Sang Eun Lee 1,∗ , Hye Rang On 1 , Hee Jung Lee 2 1 Department of Dermatology, Yonsei University College of Medicine, Seoul, South Korea 2 Department of Dermatology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
Epidermal hyaluronan (HA) and its receptor CD44 regulate permeability barrier homeostasis and skin aging. Recently, agedependent change in the metabolism of HA is suggested be responsible for these epidermal dysfunctions. Intense pulsed light (IPL) has been reported to be effective for improving photoaged skin. However, little is known about the effects of IPL on epidermal HA metabolism. We investigated whether IPL treatment can induce HA and CD44 expression in keratinocytes, which in turn contributes to improvement of age-related epidermal dysfunctions. The dorsal skin of 8 week-old (young) hairless mice and 47 week-old (aged) C57BL/6J mice was irradiated by IPL (570 nm cut-off filter, pulse interval of 20 ms, fluence 13 J/cm2 ). Before treatment and from 1–7 days after IPL treatment, the irradiated skin and unexposed skin specimens were examined. HA concentration assessed by ELISA and the mRNA levels of HABP4, CD44, and hyaluronan synthase (HAS) 3 were significantly upregulated in the epidermis of both young and old aged mice after IPL treatment, with the largest increase on day 1–3 and remained high for at least 7 days. In addition, IPL irradiation significantly increased HA content in culture supernatant of human keratinocytes and increased HAS3 and CD44 gene expression at 24–48 h after irradiation. IPL treatment also increases PCNA and filaggrin expression only in the aged mice epidermis. We demonstrated that IPL treatment increases HA and CD44 expression in epidermis and improves age-related epidermal dysfunction. These data suggest a new mechanism involved in the skin rejuvenation effect of IPL. Further studies are required to clarify the exact mechanism underlying the effect of IPL irradiation on epidermal HA metabolism. http://dx.doi.org/10.1016/j.jdermsci.2016.08.403 P05-22[O1-10] Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis Makiko Kido-Nakahara 1,∗ , Khudishta M. Aktar 1 , Masutaka Furue 1,2 , Takeshi Nakahara 2 1
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2 Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Endothelin 1 (ET-1) has been reported to evoke histamineindependent pruritus inmammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin
e135
inflammation of AD. To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and AD patients, and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line. We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and AD patients. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by either ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by either an endothelin A receptor antagonist, ERK1/2, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor. These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis in AD, which may be a future target for anti-pruritic agents. http://dx.doi.org/10.1016/j.jdermsci.2016.08.404 P05-23[O1-11] Regulatory roles of Syk in epidermal keratinocyte differentiation Nan-Lin Wu 1,2,∗ , Duen-Yi Huang 3 , Wan-Wan Lin 3 1
Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan 2 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 3 Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, is well recognized as a crucial regulator in the proximal signaling of diverse innate and adaptive immunoreceptors. More and more studies have demonstrated its expression in various cell types and also revealed its pleiotropic biologic functions in different immunological or malignant diseases. Drug design via targeting Syk is under development and has been applied in clinical trials. Epidermal keratinocytes of skin continuously undergo terminal differentiation, and such process is actually associated with defensive immunity. The expression of Syk in skin can be detected but the known functions of Syk in skin are still limited. Herein, we tried to explore the regulatory roles of Syk in keratinocyte differentiation by using primary human epidermal keratinocytes as the cell model and investigating the human specimens as well. In immunohistochemical studies, we found expression of Syk and phosphorylated Syk could be detected in normal skin tissue but the expression levels were reduced in the uppermost part of epidermis. In differentiating keratinocytes induced by phorbol 12-myristate 13-acetate and cell confluence, the expression of Syk and phosphorylated Syk were also suppressed. After treatment of Syk inhibitors or knocking down Syk in keratinocytes, the induction of mRNA and protein of various differentiation markers by cell confluence could be further enhanced. This study disclosed the in vivo expression pattern of Syk in skin and also unraveled the regulatory role of Syk in epidermal keratinocyte differentiation. These findings not only extend the current understanding of Syk in skin but also reveal the potential effects of Syk inhibitors in the treatment of skin diseases. http://dx.doi.org/10.1016/j.jdermsci.2016.08.405