Ai-Young Lee

Dongguk University, Sŏul, Seoul, South Korea

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Publications (39)118.67 Total impact

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    ABSTRACT: Cadherin 11 (CDH11) was identified as a target of miR-675 by using a luciferase reporter assay. CDH11 expression and miR-675 expression were inversely correlated. CDH11 expression was not detected in melanocytes, but CDH11 expression in fibroblasts and keratinocytes positively influenced melanogenesis via the canonical Wnt and AKT activation pathways in cocultured melanocytes. CDH11 in fibroblasts or keratinocytes induced N-cadherin and Twist1 expression, while decreasing E-cadherin expression. This suggests a role for CDH11 in epithelial-mesenchymal transition. CDH11 in fibroblasts also induced the migration of cocultured melanocytes. N-cadherin knockdown abolished the tyrosinase expression that was induced in CDH11-overexpressing fibroblasts. Collectively, our data indicate that CDH11 in fibroblasts and keratinocytes is a target of miR-675, and could be involved in melanogenesis through the induction of N-cadherin during epithelial-mesenchymal transition.Journal of Investigative Dermatology accepted article preview online, 18 June 2014; doi:10.1038/jid.2014.257.
    The Journal of investigative dermatology. 06/2014;
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    ABSTRACT: Skin irritation is one of the most common adverse reactions in hydroquinone (HQ) and retinoic acid (RA). Although melanocytes have rarely been considered to be involved in skin irritation, RA and particularly HQ could induce melanocyte toxicity, resulting in depigmentation. We chose S100B as a candidate gene for melanocytotoxicity from a genome-wide transcriptional profiling analysis after applying irritant doses of HQ, RA, and sodium lauryl sulfate (SLS) to cultures of keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte viability and cytotoxicity was examined. S100B was detected in melanocytes, but not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing concentrations of HQ, RA, SLS, and urushiol showed significant increases in intracellular and extracellular S100B expression with reduced viable cell number and increased release of lactate dehydrogenase. No RAGE expression and no significant function of CD166/ALCAM in melanocyte survival and cytotoxicity favored the role of intracellular S100B in chemically irritated melanocytes. S100B knockdown increased apoptosis through inhibition of PI3K/AKT, NF-κB, and ERK activation, suggesting the increased intracellular S100B expression by chemical irritation as a compensatory reaction to reduce cytotoxicity. The numerical decrease in S100B/c-kit-double positive melanocytes was also examined in human skin epidermis irritated by HQ or RA with stronger staining intensities of S100B. Collectively, the decrease in viable cell number by reduced intracellular S100B levels in vitro and by chemical irritation in vivo suggests that S100B could be a potential biomarker for melanocytes cytotoxicity. This article is protected by copyright. All rights reserved.
    Experimental Dermatology 01/2014; · 3.58 Impact Factor
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    ABSTRACT: Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative, is a potent anti-melanogenic agent. In addition, we proposed an alternative screening strategy to identify valiolamine derivatives with high skin permeability that act as anti-melanogenic agents when applied topically. In this study, we synthesized several valiolamine derivatives with enhanced lipophilicity and examined their inhibitory effects in a human skin model. N-(2-hydroxycyclohexyl)valiolamine (HV) possesses a stronger inhibitory effect on melanin production than voglibose in a human skin model, suggesting that HV is a more potent anti-melanogenic agent for the skin.
    International Journal of Molecular Sciences 01/2014; 15(7):12188-95. · 2.46 Impact Factor
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    ABSTRACT: H19 non-coding RNA downregulation stimulates melanogenesis in melasma patients. However, its mechanism is unclear. In this study, the potential role of a H19 microRNA, miR-675, in melanogenesis was examined. Real-time PCR using cultured normal human skin keratinocytes, melanocytes, and fibroblasts with or without H19 knockdown showed accompanying changes between expression levels of H19 and those of miR-675 in keratinocytes. MiR-675 was also detected in concentrated culture supernatants and showed expression levels parallel with those of cell lysates. In addition to RNase resistance, FACS analysis showed anti-CD63-positive exosomes in culture supernatants, suggesting miR-675 could be released extracellularly and delivered to neighboring cells without degradation. In western blot analysis, the miR-675 mimic reduced the expression of microphthalmia-associated transcription factor (MITF) and phosphorylation of cAMP-responsive element-binding protein, extracellular signal-regulated kinase and apoptosis signal-regulating kinase, whereas these expressions were increased by the miR-675 inhibitor. Although H19 was not a miR-675 target, luciferase reporter assay showed a direct binding of miR-675 to 3'-untranslated region of MITF. In addition, localized in vivo miR-675 overexpression in mouse using a cationic polymer transfection reagent showed reduced mRNA expression levels of MITF, tyrosinase, tyrosine-related protein-1 (Trp-1), and Trp-2. Collectively, the results suggest that miR-675 derived from keratinocytes could be involved in H19-stimulated melanogenesis using MITF as a target of miR-675.Journal of Investigative Dermatology advance online publication, 12 December 2013; doi:10.1038/jid.2013.478.
    Journal of Investigative Dermatology 11/2013; · 6.19 Impact Factor
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    ABSTRACT: There exists a treatment challenge with periungual warts. Topical immunotherapy with diphenylcyclopropenone (DPCP) has recently been reported to be an effective treatment for recalcitrant warts, including periungual types. We aimed to evaluate the effectiveness and preference of topical immunotherapy with DPCP in treating periungual warts. Twenty-seven patients with periungual warts who were treated with DPCP immunotherapy (2007 through 2010; Dongguk University Ilsan Hospital, Goyang, Korea) were retrospectively recruited. Other treatment modalities were also used in some patients. Lesions were grouped into the types according to the following locations: proximal nail fold, lateral nail fold and hyponychium. Total and group clearance rates as well as treatment periods according to location and disease duration were evaluated. A patient questionnaire was performed to assess the satisfaction for the treatments in those who received multiple therapies. Total success rates were 85% (by subjects) and 91% (by individual lesions). Success rate and treatment period for proximal nail fold type seemed more desirable than other locations. Success rate decreased and treatment period increased as disease duration increased. The questionnaire revealed a significantly higher satisfaction rate for DPCP immunotherapy than for cryotherapy and pulsed-dye laser. Topical immunotherapy with DPCP is an effective and preferred method in the treatment of periungual warts.
    Annals of Dermatology 11/2013; 25(4):434-9. · 0.61 Impact Factor
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    ABSTRACT: A fixed drug eruption (FDE) is not difficult to diagnose, given its clinical characteristics. However, the causative agent can be difficult to identify, particularly when the patient denies ingestion of any drugs. To the best of our knowledge, we present herein the first reported case of an FDE caused by antibiotics taken in food; doxycycline and erythromycin contained in pork and fish. A 57-year-old female experienced repeated episodes of well-demarcated erythematous patches covering her entire body. She denied taking any medications, but she thought that the lesions appeared after consuming pork and/or fish. An oral provocation test showed positive results for doxycycline and erythromycin, commonly used antibiotics in live-stock farming and in the fishing industry. Because of the antibiotics' thermostability, cooking does not guarantee the elimination of residual drugs. From the patient's history, we concluded that doxycycline and erythromycin contained in the pork and fish that she ate were the cause of the FDE.
    Allergy, asthma & immunology research 09/2013; 5(5):337-9. · 2.65 Impact Factor
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    ABSTRACT: Light emitting diode (LED) phototherapy is an effective alternative for the treatment of inflammatory skin disorders. Tacrolimus (FK-506) is a potent immunomodulating agent, which has been used to treat AD. Combination therapy is often used in the treatment of AD to improve therapeutic efficacy or to reduce the dose of each drug. To investigate the therapeutic efficacy of monotherapy with either 850nm LED phototherapy or low-dose FK-506, and combination therapy in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with LED (10 and 25J/cm(2)) alone, low-dose FK-506 (1mg/kg) or in combination. The synergistic effects of combined therapy were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, such as IgE, NO, Th2-mediated cytokines and chemokines. Combination therapy with 850nm (25J/cm(2)) LED and low-dose FK-506 showed a significant reduction in the severity of skin lesions. Combined therapy decreased in the serum level of IgE, NO, and in the splenic level of Th2-mediated cytokines and chemokines. Combination therapy significantly also reduced the inflammatory cellular infiltrate into the skin lesions. Moreover, combination therapy led to recovery of skin barrier function in the skin lesions. The use of combination of LED phototherapy and low-dose immunosuppressant improved Df-induced AD-like skin lesions in an NC/Nga mouse model by dominantly reducing IgE, NO, suppressing Th2-mediated immune responses, and inhibiting inflammatory cells, as well as improving skin barrier function.
    Journal of dermatological science 06/2013; · 3.71 Impact Factor
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    ABSTRACT: Genetic susceptibility is involved in the pathogenesis of vitiligo. Association studies with a whole genome-based approach instead of a single or a few candidate genes may be useful for discovering new susceptible genes. Although the etiology of non-segmental and segmental types is different, the association between gene polymorphisms and vitiligo has been reported, without defining types or in non-segmental type. Whole genome-based single nucleotide polymorphisms (SNPs) were examined in patients with non-segmental and segmental types of vitiligo using the Affymetrix GeneChip 500K mapping array, and 10 functional classes of significant SNPs were selected. Genotyping and data analysis of selected 10 SNPs was performed using real-time PCR. Genotype and allele frequencies were significantly different between both types of vitiligo and three of the target SNPs, DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758). A stronger association was suggested between the mutation in KIAA1005 (rs3213758) and the segmental type compared to the non-segmental type of vitiligo. DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758) may be new vitiligo-related SNPs in Korean patients, either non-segmental or segmental type.
    Journal of Korean medical science 05/2013; 28(5):775-9. · 0.84 Impact Factor
  • Ai-Young Lee, Minsoo Noh
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    ABSTRACT: Abnormal pigmentation, particularly hyperpigmentation, is major issue of concern for people with colored skin. Several hypopigmenting agents, which exert their action by inhibiting tyrosinase activity and/or transcription, have been used for treatment. However, results have been discouraging. To manage abnormal pigmentation properly, the mechanisms of melanogenesis should be understood. Endogenous and exogenous factors affect melanogenesis via intracellular machineries. cAMP and PKC are critical factors of important transduction pathways and cross-talk between them could amplify the melanogenic effect. Here, factors involved in melanogenesis regulation via cAMP and/or PKC pathways are reviewed with their action mechanisms.
    Archives of Pharmacal Research 04/2013; · 1.54 Impact Factor
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    ABSTRACT: Glucosamine (GlcN), like N-acetylglucosamine (GlcNAc), is salvaged into the hexosamine pathway and is converted to UDP-GlcNAc. Golgi N-glycan branching enzymes produce N-glycans, using UDP-GlcNAc as a substrate, which attach to the T cell receptor (TCR) and cytotoxic T lymphocyte antigen-4 (CTLA-4). These findings suggest that GlcN exerts the immunoregulation through TCR signaling, which could be involved not only in cytokine production but also activated T cell apoptosis. In fact, a preliminary study showed that GlcN reduced the number of CD3+ T cells of NC/Nga mice with AD-like skin lesions. Therefore, whether apoptosis of T cells would be one of the potential molecular mechanisms of GlcN-induced immunosuppression was investigated. Cultured human primary along with Jurkat T cells and purified T cells from NC/Nga mice with or without Df-induced AD-like skin lesion were used for the study. GlcN treatment increased the number of T cells expressing β1,6GlcNAc-branched N-glycans, with reduced ZAP-70 phosphorylation and enhanced CTLA-4 expression. GlcN treatment reduced the number of activated T cells from both the human primary and Jurkat cells and the dermatitis-induced mice. The expression of FasL and activated caspases, particulary caspase-3, was increased, whereas the phosphorylation of PI3K, Akt and NF-κB was decreased by GlcN treatment. Therefore, in addition to down-regulating TCR signaling and promoting CTLA-4 expression, GlcN may also suppress T cell function by enhancing apoptosis of activated T cells, through both extrinsic and intrinsic apoptotic signaling pathways, which were regulated by the inhibition of PI3K/Akt and NF-κB phosphorylation. This article is protected by copyright. All rights reserved.
    Scandinavian Journal of Immunology 04/2013; · 2.20 Impact Factor
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    ABSTRACT: Topical all-trans-retinoic acid (tretinoin) prevents skin atrophy induced by long-term use of topical corticosteroids, without abrogating their anti-inflammatory effects. The goal of this study was to determine the efficacy of tretinoin plus topical corticosteroids (tretinoin plus) for repigmentation in patients with vitiligo. A placebo-controlled, paired-comparison, left-right study was conducted for a period of 6 months on tretinoin plus and the vehicle plus the same topical corticosteroid (vehicle plus) treatment in 50 patients diagnosed with generalized vitiligo. Clinical responses were assessed using the computerized analysis, and the results were compared with the visual analysis. The percentage agreement between the 2 analyses was 91.8%. Among 49 participants who successfully completed this study, 27 (55%) showed a better response to tretinoin plus than to vehicle plus. The improved response was noted at an early stage of treatment, during the first 3 months in 60% of patients. Combined therapy with tretinoin plus topical corticosteroids is safe and effective and provides another option for treatment of patients with vitiligo. J Drugs Dermatol. 2013;12(4):e63-e67.
    Journal of drugs in dermatology: JDD 04/2013; 12(4):E63-e67. · 1.16 Impact Factor
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    ABSTRACT: Background Melanocytes involved in vitiligo may have inherent aberrations that make them vulnerable to extracellular insult. Allergic contact dermatitis (ACD) has been implicated in the development and progression of vitiligo. This study was conducted to investigate the association between ACD and vitiligo. Methods A total of 125 patients with vitiligo, who showed lesions in particular locations, onset at an older age, and/or pre-existing inflammation or pruritus, were included. Patch tests were performed using a Korean standard series. In order to investigate the association between avoidance of allergen and clinical improvement, 43 vitiligo patients who showed positive reactions to the patch test completed a questionnaire administered by telephone and self-assessed the status of their condition using a 10-point scale. Results A total of 98 (78.4%) of 125 patients with vitiligo showed positive patch test reactions to at least one antigen. Although a limited number of contact allergens may have specific predilection sites, a significant association (P = 0.002, odds ratio 3.06) was found between lesions distributed on the scalp and/or hairline and a positive patch test reaction to paraphenylenediamine (PPD). A positive correlation (P = 0.03) was also detected between avoidance of allergen and improvement of vitiligo lesions. Conclusions Causative allergens of ACD may play a role in the development and/or aggravation of vitiligo.
    International journal of dermatology 03/2013; · 1.18 Impact Factor
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    ABSTRACT: Combination therapy is often used in the treatment of atopic dermatitis (AD) to improve clinical efficacy or to spare the dose of each drug. Cyclosporine A (CsA) is a calcineurin inhibitor that was developed for the treatment of AD. Glucosamine (Glu) is a potent immunosuppressant that inhibits Th2-mediated immunity. We previously reported that Glu has an ameliorative effect on the development of the pathology in NC/Nga mice. The aims of our study were to investigate the therapeutic efficacy of combination of Glu and low-dose CsA in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with Glu (500mg/kg) alone, low-dose CsA (2, 5, and 10mg/kg) or in combination. The clinical scores were reduced significantly by the combination treatment with Glu and low-dose CsA. The suppression of dermatitis by combined therapy was accompanied by decrease in the plasma level of IgE and in the splenic level of IL-4, IL-5, IL-13, TARC and eotaxin. Histological analysis of the skin also revealed that combination treatment significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Particularly, immunological evaluation reveals an increase of CD4(+)CD25(+) Treg cells in the combined treatment. The induction of TSLP, which leads to systemic Th2 response, was reduced in the skin on combination treatment. The protein expression of filaggrin and involucrin was recovered by combination treatment in the skin lesions, whereas the protein expression of keratin-10 and keratin-14 decreased in the combination treatment. Collectively, our findings suggest that combination treatment of Glu and low-dose CsA leads to the therapeutic effects in Df-induced AD-like skin lesion in NC/Nga mice through inhibition of IgE, inflammatory cellular infiltrate, and recovery of skin barrier function via a mechanism that may inhibition of Th2-mediated immune responses, in part, increment of CD4(+)CD25(+) Treg cells. These results suggest that this combined immunosuppressive treatment may provide important implications for the design of therapeutic strategies aimed at AD treatment.
    International immunopharmacology 01/2013; · 2.21 Impact Factor
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    ABSTRACT: Both glucosamine and cyclosporin have been reported to show immunomodulatory effect with inhibition of each different key transcription factor for cytokine gene expression and T-cell function. The overall purpose of this pilot study was to assess the feasibility of the combination of cyclosporin with glucosamine for the treatment of patients with atopic dermatitis. Twelve patients more than 12 years old who required systemic cyclosporin were included in the study. Two of them dropped out due to violation of medication schedule. The single (S) and combination (C) regimens were crossed over every 2 weeks without a washout period between the cross-over for 6 months. Five patients were randomly assigned to the S regimen first (SC sequence), whereas the other five were given the C first (CS sequence). The change of SCORAD index was analyzed as the primary efficacy end-point by general linear model and piecewise linear mixed model. The SCORAD index was reduced with both SC and CS sequence regimens. In particular, index reduction with the C was more than that associated with S regimen; this difference increased as time lapsed. The glucosamine combination was predicted to cause an additive decrease in the mean percent change of the SCORAD index (~6%), with decreasing interleukin (IL)-4 and IL-5 cytokine levels but without increasing treatment-related adverse events. This study suggests that the C would produce better clinical outcomes than the S regimen in patients with atopic dermatitis, although confirmatory clinical trials are warranted to determine the effect of combination.
    The Journal of Dermatology 01/2013; · 1.77 Impact Factor
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    ABSTRACT: Skin diseases can be characterized by their predominant CD4-positive T-helper (Th) cell profiles. Chronic dermatological conditions often give rise to abnormal skin pigmentation. To understand the role of Th cells in pigmentation, the effects of the major Th cell cytokines, IFNγ, IL-4, and IL-17A, on melanogenesis were evaluated using cultured normal human melanocytes (NHMs) instead of relying on transformed melanoma cell lines. IL-4 directly inhibited melanogenesis in NHMs and downregulated both transcription and translation of melanogenesis-associated genes, such as microphthalmia-associated transcription factor (MITF) and dopachrome tautomerase. Despite the lack of a direct inhibition of melanin pigment synthesis, IFNγ and IL-17A increased the synthesis of an antimelanogenic cytokine IL-6 in NHMs. IFNγ activated signal transducers and activators of transcription 1 (STAT1) and STAT3 phosphorylation in NHMs, and IL-4 increased the STAT3 and STAT6 phosphorylation. The differential phosphorylation profile of STAT proteins between IFNγ and IL-4 may explain the difference in their effect on melanogenesis in NHMs. The IL-4-induced downregulation of melanogenesis was inhibited by treating NHMs with a JAK2 inhibitor AG490 or STAT6 siRNA. In conclusion, the involvement of the IL-4-induced JAK2-STAT6 signaling and the IFNγ- or IL-17A-dependent antimelanogenic IL-6 production should be considered as one of the mechanisms explaining the association with hypopigmention in skin diseases.Journal of Investigative Dermatology advance online publication, 20 September 2012; doi:10.1038/jid.2012.331.
    Journal of Investigative Dermatology 09/2012; · 6.19 Impact Factor
  • Yu Shun Tian, Nan-Hyung Kim, Ai-Young Lee
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    ABSTRACT: Antiaging effects of light-emitting diodes (LEDs) have been clinically demonstrated using one or two wavelengths. The mechanism is unclear. To examine direct and indirect photobiomodulation effects of LEDs on narrow-band ultraviolet B (NB-UVB)-induced photoaging using seven different wavelengths alone or in combination. Four LED wavelengths were chosen based on type I collagen and metalloproteinase (MMP)-1 expression. NB-UVB-irradiated fibroblasts or keratinocytes were irradiated using these four wavelengths. The expression of collagen and MMP-1 in fibroblasts with or without conditioned medium from LED-irradiated keratinocytes and the expression of proinflammatory cytokines in the LED-irradiated keratinocytes were examined. Irradiation with four wavelengths (630, 660, 830, and 850 nm) significantly increased the number of viable fibroblasts. These four wavelengths also increased type I collagen expression, particularly four combinations (630/830, 660/850, 630/850, and 660/830 nm). The fibroblasts cultured with the keratinocyte conditioned medium, particularly with a combination of 630/850 or 660/830 nm, increased collagen levels. Low tumor necrosis factor alpha (TNF-α) and high transforming growth factor beta 1 (TGF-β1) expression was detected in the LED-irradiated keratinocytes. The combination of 630/850- or 660/830-nm irradiation led to better direct and indirect antiphotoaging outcomes than single LED wavelengths in NB-UVB-irradiated cultured normal human skin cells.
    Dermatologic Surgery 07/2012; 38(10):1695-703. · 1.87 Impact Factor
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    ABSTRACT: The pathogenesis of melasma is unknown, although the potential role of estrogen has been considered. Microarray and real-time PCR analyses revealed that upregulation of PDZ domain protein kidney 1 (PDZK1) is clinically correlated with melasma. Although there has been no report that PDZK1 is involved in pigmentation and/or melanogenesis, PDZK1 expression can be induced by estrogen. In this study, the role of PDZK1 upregulation in melasma was examined, particularly in connection with estrogen, using biopsied skin specimens from 15 patients and monocultures and cocultures of melanocytes and keratinocytes with or without overexpression or knockdown of PDZK1. Estrogen upregulated PDZK1. Overexpression of PDZK1 increased tyrosinase expression and melanosome transfer to keratinocytes, whereas PDZK1 knockdown reduced estrogen-induced tyrosinase expression, through regulation of expression of estrogen receptors (ERs) ER-α and ER-β. The PDZK1-induced tyrosinase expression and melanosome transfer was regulated by ion transporters such as sodium-hydrogen exchanger (NHE), cystic fibrosis transmembrane conductance regulator (CFTR), and SLC26A3, which showed a specific association with each ER subtype. In the melanosome transfer, PDZK1 also increased phosphorylation of ezrin/radixin/moesin (ERM) and ras-related C3 botulinum toxin substrate 1, but not the expression of proteinase-activated receptor-2. Collectively, upregulation of PDZK1 could have an important role in the development of melasma in connection with estrogen through NHE, CFTR, and SLC26A3.
    Journal of Investigative Dermatology 06/2012; 132(11):2622-31. · 6.19 Impact Factor
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    ABSTRACT: As many new cosmetic products are introduced into the market, attention must be given to contact dermatitis, which is commonly caused by cosmetics. We investigate the prevalence of preservative allergy in 584 patients with suspected cosmetic contact dermatitis at 11 different hospitals. From January 2010 to March 2011, 584 patients at 11 hospital dermatology departments presented with cosmetic contact dermatitis symptoms. These patients were patch-tested for preservative allergens. An irritancy patch test performed on 30 control subjects using allergens of various concentrations showed high irritancy rates. Preservative hypersensitivity was detected in 41.1% of patients. Allergens with the highest positive test rates were benzalkonium chloride (12.1%), thimerosal (9.9%) and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (5.5%). Benzalkonium chloride and chlorphenesin had the highest irritancy rate based on an irritancy patch test performed using various concentrations. Seven of 30 normal subjects had a positive irritant patch reading with 0.1% benzalkonium chloride and eight of 30 normal subjects had a positive irritant patch reading at 4 days with 0.5% chlorphenesin in petrolatum. Although benzalkonium chloride was highly positive for skin reactions in our study, most reactions were probably irritation. MCI/MI and thimerosal showed highly positive allergy reactions in our study. The optimum concentration of chlorphenesin to avoid skin reactions is less than 0.5%.
    The Journal of Dermatology 05/2012; 39(8):677-81. · 1.77 Impact Factor
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    ABSTRACT: Kojic acid is a fungal metabolite widely used in medicinal and cosmetic formulations as a skin-lightening agent based on its de-pigmenting activity. Although in human clinical studies kojic acid has been shown to be effective in the treatment of hyper-pigmentation disorders such as melasma, the reasons for its apparent lack of anti-melanogenic activity in cultured mammalian melanocytes are unclear. This study was aimed to elucidate pharmacological mechanisms of the in vivo anti-melanogenic activity of kojic acid in human skin. A primary human melanocyte and keratinocyte co-culture system was used to evaluate whether kojic-acid-induced changes in keratinocytes were associated with anti-melanogenic activities in melanocytes. The cytokine secretion profiles in response to kojic acid were analyzed. Kojic acid increased interleukin (IL)-6 and IL-8 production in melanocyte/keratinocyte co-cultures; however, IL-6 directly inhibited melanogenesis whereas IL-8 did not. In melanocyte monocultures, kojic acid did not increase IL-6 production whereas in keratinocyte monocultures it significantly up-regulated IL-6 gene and protein expression. Therefore, the up-regulation of IL-6 in melanocyte/keratinocyte co-cultures seems to be originated from kojic acid-induced changes in keratinocytes. Anti-IL-6 antibody treatment antagonized the anti-melanogenic effect of kojic acid on the co-cultures. The pharmacological mechanism of kojic acid to explain clinically effective anti-melanogenic activity on hyper-pigmented skin is associated with the kojic acid-induced IL-6 production in keratinocytes. The cross-talk between melanocytes and keratinocytes should be determined in future studies on the pharmacological mechanisms of clinically effective dermatological drugs acting on the epidermis.
    Journal of dermatological science 03/2012; 66(3):207-15. · 3.71 Impact Factor
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    ABSTRACT: HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as IFNγ, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human β2-defensin (HBD2) in response to IFNγ, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. IFNγ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to IFNγ, IL-4 or IL-17A.
    Biomolecules and Therapeutics 03/2012; 20(2):171-176. · 0.79 Impact Factor

Publication Stats

177 Citations
118.67 Total Impact Points

Institutions

  • 2008–2014
    • Dongguk University
      • Department of Dermatology
      Sŏul, Seoul, South Korea
  • 2012–2013
    • Ajou University
      • College of Pharmacy
      Sŏul, Seoul, South Korea
    • Yanbian University
      Yang-chi-t'eng, Jilin Sheng, China
  • 2003–2005
    • Eulji University
      • Department of Dermatology
      Sŏul, Seoul, South Korea