Serah Lee

Infrared plus visible light and heat from natural sunlight participate in the expression of MMPs and type I procollagen as well as infiltration of inflammatory cell in human skin in vivo

BACKGROUND Compared with the detailed characterization of the ultraviolet (UV) response in human skin, the effects of infrared (IR) and other regions of the sunlight are scarce. OBJECTIVES To determine the participation of IR/visible light and heat components of the sunlight on matrix metalloproteinases (MMPs) and type I procollagen expression, and inflammatory cell infiltration in human skin in vivo. METHODS The buttocks of 16 healthy volunteers (aged 24-43 years, 10 male and 6 female) were irradiated with a 1.1-3 minimal erythema dose (MED) of natural sunlight. To determine the differential effects of UV, IR/visible rays and solar heat alone, the exposed sites were covered with either a UV filter or black cloth, respectively, during irradiation. Skin samples were taken 24h later. RESULTS IR/visible light spectrum of sunlight significantly increased MMP-1 and MMP-9 expression and decreased type I procollagen expression. Solar heat also contributed to the increased MMP-1 expression. Only the UV region recruited neutrophils into the dermis, while UV, IR/visible light and heat contributed to macrophage infiltration. CONCLUSIONS IR/visible light and heat of natural sunlight, in addition to UV, play a role in modulating the expressions of MMPs and procollagen, and inflammatory cell infiltration in human skin.

Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo

BACKGROUND No studies have yet been undertaken to determine the effect of aloe gel on the clinical signs and biochemical changes of aging skin. OBJECTIVE We wanted to determine whether dietary aloe vera gel has anti-aging properties on the skin. METHODS Thirty healthy female subjects over the age of 45 were recruited and they received 2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600 mg/d) of aloe vera gel supplementation for 90 days. Their baseline status was used as a control. At baseline and at completion of the study, facial wrinkles were measured using a skin replica, and facial elasticity was measured by an in vivo suction skin elasticity meter. Skin samples were taken before and after aloe intake to compare the type I procollagen and matrix metalloproteinase 1 (MMP-1) mRNA levels by performing real-time RT-PCR. RESULTS After aloe gel intake, the facial wrinkles improved significantly (p<0.05) in both groups, and facial elasticity improved in the lower-dose group. In the photoprotected skin, the type I procollagen mRNA levels were increased in both groups, albeit without significance; the MMP-1 mRNA levels were significantly decreased in the higher-dose group. Type I procollagen immunostaining was substantially increased throughout the dermis in both groups. CONCLUSION Aloe gel significantly improves wrinkles and elasticity in photoaged human skin, with an increase in collagen production in the photoprotected skin and a decrease in the collagen-degrading MMP-1 gene expression. However, no dose-response relationship was found between the low-dose and high-dose groups.

Increased expression of 14-3-3ɛ protein in intrinsically aged and photoaged human skin in vivo

Skin aging is a complicated process associated with the passage of time and environmental exposure, especially to UV light. This aging phenomenon is related to alterations in various cellular mechanisms, such as changes in apoptosis, perturbations to cellular signaling, and an increased genetic instability. In this study, we investigated changes of proteins involved in intrinsic aging by the proteomic analysis of human sun-protected (upper inner arm) young and aged dermis. One of the proteins upregulated in aged dermis was identified as 14-3-3epsilon. This protein is an isoform of 14-3-3 protein, which is involved in cellular processes like signal transduction, cell cycle arrest, and apoptosis. 14-3-3epsilon is consistently found to be upregulated in the sun-protected dermis of aged skin, by Western blotting and immunohistochemical staining. In addition, we demonstrate that the expression of 14-3-3epsilon is further upregulated in the sun-exposed (photodamaged) dermis, and that the UV irradiation of young skin significantly upregulates 14-3-3epsilon in vivo. Our results suggest the possibility that the cellular processes related to 14-3-3epsilon protein play an important role in the photoaging and intrinsic aging of human skin.

Toll-like receptor 2 mediates a cutaneous reaction induced by repetitive ultraviolet B irradiation in C57/BL6 mice in vivo.

Toll‐like receptors (TLRs) mediate not only innate immunity against infection and but also sterile inflammation triggered by endogenous molecules. We conducted a comparative study of the different inflammatory responses induced by repetitive ultraviolet (UV) B irradiation in wild‐type (WT) and TLR2 knockout (KO) mice, to provide in vivo evidence of the role of TLRs in mediating UVB‐induced responses. UVB‐induced inflammatory responses were less severe in TLR2 KO mice than in WT mice after 6 weeks of repeated UVB irradiation. UVB‐treated TLR2 KO mice displayed less prominent erythema and scaling, and histopathology showed significantly thinner skin and less inflammatory cell infiltration than that in WT mice. UVB‐induced expression of heat‐shock protein 70 (an endogenous ligand of TLR2) was lower in TLR2 KO mice. Quantitative RT‐PCR revealed significantly lower gene expression levels of UVB‐induced interleukin (IL)‐1β, IL‐6 and matrix metalloproteinase (MMP)‐13 in TLR2 KO mice. TLR2 KO mice also showed significantly lower protein level expression of UVB‐induced IL‐1β in ELISA and MMP‐13 in Western blots. Our study demonstrated that TLR2 was associated with inflammatory responses to repetitive UVB irradiation in C57/BL6 mice. Moreover, it suggests that the role of TLR2 in the cutaneous response of UV irradiation and in developing new agents for modulating the effects of UV irradiation should be considered.

Lipid ingredients in moisturizers can modulate skin responses to UV in barrier-disrupted human skin in vivo

BACKGROUND Chemicals with a molecular weight <500 and adequate lipid solubility can penetrate the intact human skin. As many lipid ingredients in moisturizers have molecular weights <500, the lipid ingredients may penetrate into the skin and affect skin responses to UV; however, little is known about this phenomenon. OBJECTIVE To evaluate the effects of major lipid ingredients in moisturizers on skin responses to UV in tape-stripped human skin in vivo. METHODS We evaluated the effects of three major lipid ingredients in moisturizers (cholesterol, linoleic acid, and a synthetic ceramide, N-oleoyl-phytosphingosine) on skin responses to UV in the tape-stripped skin of healthy volunteers. After 2 days of lipid-application, the areas were irradiated with UV, and skin samples were obtained 24h after irradiation. Histologic features and the expression of the markers of collagen metabolism and inflammatory mediators were evaluated. RESULTS Compared to vehicle, topical cholesterol significantly decreased the degree of dermal inflammatory infiltrates and exocytosis, and also decreased the expression of MMP-1, IL-6, and IL-1ß mRNA. In contrast, topical linoleic acid increased the induction of apoptotic cells, and the expression of MMP-1 and IL-6 mRNA. N-oleoyl-phytosphingosine increased the expression of MMP-1 and IL-6 mRNA, while decreasing the expression of COX-2 mRNA. CONCLUSIONS Topical cholesterol can protect the barrier-disrupted skin against UV-induced damage, while linoleic acid or N-oleoyl-phytosphingosine alone has the potential to aggravate the damage.

Endogenous Estrogen Exacerbates UV-Induced Inflammation and Photoaging in Mice

likely by extensive cross-linking. As a first effect of the depletion of non-desmosomal Dsg1, intercellular widening occurs. Then, when the desmosomes also become depleted of Dsg1, they shrink in size and number. When the amount of anti-Dsg1 IgG increases, the IgG will spread further upward into the higher layers, also leading to intercellular widening and desmosomal reduction there. Finally, when the IgG reaches the layers where Dsg3 is absent and cannot compensate for the loss of Dsg1, desmosomes will no longer be able to form stable structures and will melt away with subcorneal acantholysis as the final result. The effects of anti-Dsg3 antibodies on the epidermis differ from those of antiDsg1 antibodies. IgG directed against Dsg3 spreads through the epidermis and leads to clustering and depletion of Dsg3 throughout the Dsg3-expressing layers. This does not, however, lead to intercellular widening or a reduction in the size and number of the desmosomes. Apparently, loss of Dsg3 is less devastating than loss of Dsg1 to the desmosomes as they retain their normal shape. This fits with observations in patients with mdPV, who have blistering of the mucous membranes but a perfectly healthy and strong skin. Although their skin is loaded with anti–cell surface IgG deposits, it does not blister, even when it is firmly rubbed to elicit the Nikolsky sign. Next, when antibodies directed against Dsg1 are also present in addition to antibodies against Dsg3 (as in mcPV), the depletion of Dsg1 will affect the desmosomes, which then start to shrink. As the desmosomes can no longer compensate for the loss of both Dsg1 and Dsg3, they will melt away in the lower layers, which eventually leads to suprabasal acantholysis. We therefore conclude that Dsg1, but not Dgs3, is necessary for preserving the normal size and number of desmosomes in the human epidermis and that loss of Dsg1 is conditional for developing cutaneous acantholysis in pemphigus.

Urban particulate matter in air pollution penetrates into the barrier-disrupted skin and produces ROS-dependent cutaneous inflammatory response in vivo

BACKGROUND Particulate matter (PM) is an integral part of air pollution, which is a mixture of particles suspended in the air. Recently, it has been reported that PM is associated with increased risks of skin diseases, especially atopic dermatitis in children. However, it is unclear if PM directly goes into the skin and what mechanisms are involved in response to PM. OBJECTIVE To see whether PM could penetrate into the barrier-disrupted skin, produce reactive oxygen species (ROS), and elicit an inflammatory response. METHODS We collected PMs during a winter in Seoul and used cultured keratinocytes for in vitro study and tape-stripped BALB/c mice for in vivo study. RESULTS Keratinocyte cytotoxicity increased in a dose-dependent manner by PM treatment. IL-8 and MMP-1 mRNA expression and protein levels were significantly increased compared to control by qPCR and ELISA, respectively. Cellular ROS production was increased by PM treatment, and antioxidant N-acetyl cysteine pretreatment prevented induction of inflammatory cytokines IL-8 and MMP-1. In PM-treated keratinocytes, electron-dense subcellular particles were observed by transmission electron microscopy. PM was observed inside hair follicles in both intact and barrier-disrupted skin in vivo. Additionally, intercellular penetration of PM was seen in the barrier-disrupted skin. Repeated PM application induced epidermal thickening and dermal inflammation with neutrophil infiltration. Finally, N-acetyl cysteine could ameliorate skin inflammation induced by PM application. CONCLUSION PM penetrates into the barrier-disrupted skin, causing inflammation, demonstrating detrimental effects in the skin.

Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear hormone receptor involved in the transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant enzymes such as catalase, whose expression is decreased in aged human skin. Here we investigated the expression of PPARα in aged and ultraviolet (UV)-irradiated skin, and whether PPARα activation can modulate expressions of matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We found that PPARα mRNA level was significantly decreased in intrinsically aged and photoaged human skin as well as in UV-irradiated skin. A PPARα activator, Wy14643, inhibited UV-induced increase of MMP-1 and decrease of procollagen expression and caused marked increase in catalase expression. Furthermore, production of reactive oxygen species (ROS) was suppressed by Wy14643 in UV-irradiated and aged dermal fibroblasts, suggesting that the PPARα activation-induced upregulation of catalase leads to scavenging of ROS produced due to UV irradiation or aging. PPARα knockdown decreased catalase expression and abolished the beneficial effects of Wy14643. Topical application of Wy14643 on hairless mice restored catalase activity and prevented MMP-13 and inflammatory responses in skin. Our findings indicate that PPARα activation triggers catalase expression and ROS scavenging, thereby protecting skin from UV-induced damage and intrinsic aging.

Blood type B antigen modulates cell migration through regulating cdc42 expression and activity in HaCaT cells.

ABO blood group is determined by carbohydrate antigens, called ABH antigens. It has been known that the change of carbohydrate antigen expression, including ABH antigens, has correlation with the tumor metastasis and survival; however, the exact mechanism remains to be elucidated. ABH antigens are expressed not only in blood cells but also in several tissues. In epidermis, ABH antigen is expressed in the uppermost spinous and granular layer. We investigated the role of ABH antigens on the cell migration of HaCaT keratinocytes, which express B antigen. Knock‐down of B antigen expression by small interference RNA of FUT1 inhibited HaCaT cell migration. At that time, we found that lamellipodia and actin fiber were also reduced by knock‐down of B antigen expression. The transcription of cdc42, a kind of Rho GTPase which plays a key role in actin polymerization, was reduced by down‐regulated B antigen expression. Furthermore, the reduced B antigen expression also inhibited the interaction of cdc42 and N‐WASP. Collectively, our data provide a clue how ABH antigens regulate the cell migration mechanism. J. Cell. Physiol. 228: 2243–2251, 2013.

Deeper Wrinkle Formation and Less Melanin Production in Aged Korean Women with B Blood Type

364 Ann Dermatol Received October 17, 2016, Revised April 13, 2017, Accepted for publication June 5, 2017 Corresponding author: Jin Ho Chung, Department of Dermatology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel: 82-2-2072-2414, Fax: 82-2-742-7344, E-mail: jhchung@snu.ac.kr ORCID: https://orcid.org/0000-0003-0520-0266 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright