Effect of topical application of quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice.

BACKGROUND: Quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside (QGR) is a new quercetin derivative which is isolated from the leaves of Acer ginnala Maxim, a native plant of Korea. Quercetin has several biological effects including antioxidative, anti-inflammatory, and anti-allergic effects. However, the topical effect of QGR on atopic dermatitis (AD) like skin lesion in NC/Nga mice has not been studied. OBJECTIVE: To evaluate the anti-inflammatory and anti-allergic effect of QGR in a murine model of atopic dermatitis. METHODS: We measured inducible nitric oxide synthase (iNOS) and cyclooxygenase -2(COX-2) level in RAW264.7 cell with QGR treatment. And after induction of AD like skin lesions with Dermatophagoides farina (Df) ointment, mice were treated with QGR and control drugs. Clinical scores, interleukin (IL) 4, 5, and 13, serum IgE, eosinophil levels, iNOS and COX-2 level were evaluated. RESULTS: Results show that mRNA level of iNOS and COX-2 in vitro were decreased after QGR treatment. Topical QGR markedly decreased the iNOS and COX-2 mRNA expressions in the skin. QGR also significantly suppressed the increase in the level of total plasma IgE and eosinophils. In addition, topical application of QGR down-regulated the expressions of the cytokines, IL-4,5 and 13, which were induced by Df ointment stimulation. CONCLUSIONS: In the present study, we showed that topical application of QGR ameliorated Df-induced AD-like inflammatory responses in NC/Nga mice. These results demonstrate that QGR might be beneficial in the treatment of AD.

Calcitriol May Down-Regulate mRNA Over-Expression of Toll-Like Receptor-2 and -4, LL-37 and Proinflammatory Cytokines in Cultured Human Keratinocytes.

BACKGROUND: Although vitamin D analogs have been used in the topical treatment of psoriasis, their mechanisms of action are not well understand. Calcitriol, the hormonally active vitamin D3 metabolite, has been demonstrated to exert immunomodulatory effects in the skin by down-regulating the expression of Toll-like receptors (TLRs) and proinflammatory cytokines. OBJECTIVE: We investigated the effects of calcitriol on the expression of TLR2, TLR4, antimicrobial peptide LL-37, and proinflammatory cytokines in cultured human keratinocytes. METHODS: The mRNA expression levels of TLR2, TLR4, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and LL-37 in cultured human keratinocytes were measured by real-time polymerase chain reaction (PCR) and reverse transcription (RT). Furthermore, we measured supernatant TNF-α levels by an enzyme-linked immunosorbent assay (ELISA) to confirm the effects of calcitriol on TLR2 and TLR4. RESULTS: As measured by RT-PCR and real-time PCR, calcitriol was found to suppress the lipopolysaccharide- and ultraviolet B radiation-mediated induction of expression of TLRs, LL-37 and proinflammatory cytokines such as TNF-α and IL-1ß in normal human keratinocytes. The supernatant TNF-α levels measured by ELISA were also suppressed after treatment with calcitriol. CONCLUSION: Calcitriol may down-regulate inflammatory stated over-expression of LL-37 and proinflammatory cytokines.

Topical application of Rosa multiflora root extract improves atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.

The roots of Rosa multiflora THUNB. (RM) has been used in oriental traditional medicines as remedies for scabies, rheumatic arthralgia and stomatitis which were practicably related with today's inflammatory and allergic diseases. In the present study, we evaluated whether RM root extract (RME) and its major constituent, 2-(3,4-dihydroxyphenyl)-6-(4-hydroxyphenyl)-8-(2,4-dihydroxyphenyl)-2,3-trans-6,7-cis-7,8-trans-3,4,7,8-tetrahydro-2H,6H-pyrano[2,3-f] chromene-3,7,9-triol (RM-3) belongs to condensed tannins, improve atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by mite antigen. Topical application of RME as well as RM-3 improved skin severity and suppressed mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) on skin tissues, in addition, significantly reduced T helper 2 (Th2) immune responses via interleukin 10 (IL-10) up-regulation. Thus, RME, contains lots of condensed tannins such as RM-3 which possesses potent anti-inflammtory and immune-modulatory effects, may be useful for treatment of skin allergies and can be developed as new alternative herbal therapy against AD.

Time-dependent progression from the acute to chronic phases in atopic dermatitis induced by epicutaneous allergen stimulation in NC/Nga mice.

Atopic dermatitis (AD) is a complicated skin condition influenced by genetic background and environmental factors. In this study, we applied Dermatophagoides farinae body extract (DfE) to the barrier-disrupted skin of NC/Nga mice twice a week for 8 weeks to identify the clinical and immunological factors in AD progression. Repeated application of the DfE to the skin of NC/Nga mice showed the similar consequences for the natural course of progression in human AD, histologically and immunologically. We confirmed that the AD-like skin lesions in NC/Nga mice did not last for the whole period of our experiment in spite of repeated topical applications of DfE twice a week. Topical DfE stimulation increased the skin mRNA expressions of Th1-, Th2- and Th17-related cytokines in the acute phase. The expression patterns of IL-4 and IL-13 in splenic T cells and skin lesions were consistent with the time course alterations of clinical features of AD-like skin symptoms. We also showed that there was a remission phase either just before or right after the chronic phase in this experimental model. Interestingly, splenic T-cell-derived IL-5 expression began to increase in the chronic phase, while skin-derived IL-5 mRNA expression increased in the acute phase. In conclusion, our results suggest that we should pay attention to the characteristics of each stage of AD progression and choose a suitable corresponding stage of animal model not only to elucidate the pathogenesis of AD but also to develop and evaluate therapeutic drugs for AD.

The changing pattern of parasitic infection among Korean populations by paleoparasitological study of Joseon Dynasty mummies.

In the coprolites of 4 recently discovered Joseon mummies of Korea, we found Ascaris lumbricoides , Trichuris trichiura , Metagonimus yokogawai , Paragonimus westermani , and Clonorchis sinensis eggs. The current finding was compared with previous paleoparasitological data, and with recent national survey data from Korea. For A. lumbricoides and T. trichiura , similar patterns of infection prevalence were observed between the national survey of 1961 and our current Joseon data. Some of the trematode species (C. sinenesis and P. westermani) showed much higher infection prevalences among the Joseon Koreans than among their 1960s descendants. The present results indicate that the decrease in trematode infection rates might have begun earlier than was the case for nematode infection.

Aggravation of atopic dermatitis-like symptoms by consecutive low concentration of formaldehyde exposure in NC/Nga mice.

Formaldehyde (FA) has been known to be associated with development of asthma (AS) and atopic dermatitis (AD). In this study, we investigated whether FA inhalation would affect the provocation or exacerbation of AD-like symptoms. Atopic-prone NC/Nga mice were exposed to low (0.2 ppm) and high (1.0 ppm) concentration of FA by inhalation. Combined exposure to low concentration of FA inhalation and topical house dust mite (HDM) stimulation significantly upregulated HDM-induced total plasma IgE and IgG2a production, Th1-, Th2-, Th17-related cytokine as well as COX-2 mRNA expressions in the skin. Interestingly, independent FA inhalation, especially at low concentration (0.2 ppm), increased the skin mRNA expressions of IL-13, IL-17E/IL-25 and COX-2, even though it failed to induce AD-like skin inflammation. In conclusion, we suggest that increased skin mRNA expressions of IL-13, IL-25/IL-17E and COX-2 by independent low concentration of FA exposure might be a key factor to exacerbate HDM-mediated AD-like skin inflammation.

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice.

BACKGROUND: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T). METHODS: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed. RESULTS: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils. CONCLUSION: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.

Genetic Polymorphism of FLG in Korean Ichthyosis Vulgaris Patients.

BACKGROUND: Filaggrin is a key protein that facilitates the formation of skin barrier by forming a stratum corneum. Mutations in the gene encoding filaggrin (FLG) have recently been reported in patients with ichthyosis vulgaris (IV). Interestingly, there are ethnic differences between FLG mutations identified in Asians and Europeans, and few FLG mutations are overlapping between Chinese and Japanese IV patients. OBJECTIVE: The aim of this study was to investigative the genetic polymorphism of FLG in Korean IV patients. METHODS: Genomic DNA was extracted from whole venous blood specimen of Korean patients with IV and a control group, and the full sequence of FLG was determined via overlapping long-range polymerase chain reaction method. RESULTS: Analysis of base sequence previously unreported reveal new nonsense mutation p.Y1767X in a Korean IV patient, and additional new single nucleotide polymorphisms. CONCLUSION: On the basis of this study, it is anticipated that analysis of FLG gene sequence be extended to other dermatoses associated with FLG, such as atopic dermatitis.

Topical application of two condensed tannins from the root of Rosa multiflora Thunberg for the treatment of atopic dermatitis (AD) in NC/Nga mice.

Recently, the isolation of several condensed tannins from the roots of Rosa multiflora Thunberg, a traditional herbal therapy in oriental medicine for rheumatoid arthritis and scabies, was described. Two of the major condensed tannins - procyanidin B-3 (ProB3) and ent-guibourtinidol-(4ß â†’ 6)-catechin (RM-1) - were then applied topically to atopic dermatitis-like skin lesions on NC/Nga mice in order to assess their immunomodulatory properties. Both ProB3 and RM-1 significantly reduced the serum levels of eosinophils, IgE and certain Th2 cytokines (IL-4, 5 and 13) (p < 0.05 or 0.01). Additionally, ProB3 and RM-1 significantly reduced both the mRNA and protein expression of COX-2 and iNOS in mouse skin tissues (p < 0.01). Such results strongly suggest that ProB3 and RM-1 may be useful in the treatment allergic skin conditions, most notably atopic dermatitis.

Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by phenolic compounds from roots of Rhododendron mucronulatum.

The roots of Rhododendron mucronulatum Turzaninov have been used in Oriental traditional medicine for the treatment of dysuria, fever, increase of digestive activity and tonics in China and Korea. Activity guided isolation of the roots of Rhododendron mucronulatum Turzaninov has led to the isolation of three flavonoids, one flavan 3-ol and one proanthocyanidin. Chemical investigation of the 80% Me2 CO extract from the roots of Rhododendron mucronulatum led to the isolation and identification of five compounds: taxifolin (1), taxifolin 3-O-ß-D-glucopyranoside (2), quercetin 3-O-α-L-arabinofuranoside (3), (-)-epicatechin (4), procyanidin B-3 (5). To investigate the antioxidative and antiinflammatory effects of these compounds, their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated HaCaT cells were also quantified by western blotting and their end products, nitric oxide (NO) and prostaglandin E2 (PGE2 ), respectively. Compounds (1-5) showed potent DPPH radical scavenging compared with positive controls (L-ascorbic acid). Also, compounds 1 and 2 dose-dependently inhibited the expressions of inflammatory mediators, NO and PGE2 , suggesting they are promising candidates as antiinflammatory agents.

Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice.

AIM OF THE STUDY: The bark of Alnus species has long been used in traditional oriental medicine in the treatment of many pathological conditions, including fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic herpes, eczema and prurigo), and inflammation. In order to assess the immunomodulatory efficacy of a novel herbal medicine in treating atopic dermatitis, we measured serum levels of several allergic and inflammatory biomarkers in NC/Nga mice before and after treatment with this experimental agent. MATERIALS AND METHODS: Gene and protein expression analyses of iNOS and COX-2 were quantified by real time PCR and Western blot analysis and serum levels of IL-4, -5 and -13 were also measured by ELISA, all of which were reduced after treatment with the experimental agent. Additionally, serum concentrations of IgE and blood eosinophil counts were reduced in treated mice. RESULTS: The topical application of leaf and bark extract from Alnus japonica suppressed the development of AD-like skin lesions. The percent of blood eosinophils was decreased after treatment with leaf and bark extract from Alnus japonica. The serum IgE and Th2-related cytokine levels were decreased after treatment with leaf and bark extract from Alnus japonica compared with those treated with base cream (vehicle treated AD group). The IL-4, IL-5 and IL-13 were lower than those of vehicle treated AD group. CONCLUSIONS: We contend that leaf and bark extract from Alnus japonica may prove useful in the treatment of atopic dermatitis and other allergic skin diseases, although more in-depth clinical studies are necessary before clinical implementation.

Significant damage of the skin and hair following hair bleaching.

Scalp burns can be caused by hair bleaching with excess procedures such as unnecessary heating and excessive treatment with bleaching agents. The aim of this study was to investigate the morphological and histological changes of the hair and skin after bleaching. Ammonium persulfate and hydrogen peroxide (6% or 9%) solution mixed at a ratio of 1:2 (weight ratio) were sufficiently applied to human hairs and rat skin. The bleached hairs were brightened up to yellow by increasing the concentration of hydrogen peroxide and time of bleach treatment. After bleaching, scanning electron microscopy (SEM) was used to observe that the cuticle scales of the hairs were irregular and lifted. The mechanical properties of the bleached hairs, such as tensile strength and elongation, were slightly different than the untreated hairs. The tested rat skin showed severe swelling after treatment of the bleaching agent (9% hydrogen peroxide). The rat skin bleached with 9% hydrogen peroxide exhibited epidermal thinning and subepidermal vesicle formation. The extracellular matrix of the skin was seriously disrupted after bleaching. Therefore, the use of only suitable bleaching procedures is suggested in order to avoid injuries.

Changes of antimicrobial peptides and transepidermal water loss after topical application of tacrolimus and ceramide-dominant emollient in patients with atopic dermatitis.

Increased transepidermal water loss (TEWL) and downregulated antimicrobial peptides (AMPs) are observed in patients with atopic dermatitis (AD). Tacrolimus and ceramide-dominant emollients are effective in the treatment of AD by preventing the production of inflammatory cytokines and by correcting skin barrier dysfunctions, respectively. Present study was designed to investigate the relationship between antimicrobial and barrier factors by measuring the changes of AMPs and TEWL after topical application of tacrolimus and ceramide-dominant emollient in the patients with AD. A total of three patients with AD were treated with tacrolimus in one lesion and ceramide-dominant emollient in another lesion for 4 weeks. RT-PCR and western blotting revealed that the mRNA and protein expression levels of hBD-2 and LL-37 were increased on the both study sites. Immunohistochemical analysis showed significant increase of AMPs and IL-1alpha, while, IL-4 was decreased on the both study sites. The mean changes of TEWL and AMPs showed no statistical difference between both sites. Tacrolimus and ceramide-dominant emollient influence on both TEWL and AMPs expression in patients with AD, namely they have similar effects on both of the two. This study shows that restoration of permeability barrier function is accompanied by the concomitant improvement of antimicrobial defense in patients with AD.

Facilitated skin permeation of oregonin by elastic liposomal formulations and suppression of atopic dermatitis in NC/Nga mice.

To develop an external preparation of oregonin (ORG) for the treatment of atopic dermatitis (AD), conventional creams (CC) and elastic liposomes (EL) containing ORG have been formulated and examined for their in vitro skin permeation properties and in vivo therapeutic efficacy assessments. EL, consisting of soybean phosphatidylcholine and Tween 80 (85 : 15 w/w %), were of flexible nanocarriers: they were about 130 nm in size and had a 4-fold greater deformability index than conventional liposomes. In a skin permeation study using a Franz diffusion cell mounted with depilated mouse skin, liposomal systems were superior to cream, revealing greater flux values. Both CC and EL were diversified with the addition of Trans-activating transcriptional activator (Tat) peptide, a sort of cell penetrating peptide, and subjected to in vivo efficacy evaluations in NC/Nga mice with AD-like lesions. On clinical observation for skin severity, rapid and profound improvement was observed in the treatment group with Tat-added liposomes (EL/T), showing a significant difference (p<0.05) versus Tat-added cream. The results indicated that EL/T treatment is effective for normalizing the immune-related responses and alleviating AD, evaluated as changes in the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-4, immunoglobulin E (IgE), and eosinophils in skin or blood.

Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice.

The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1beta, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real-time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX-2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.

Atopic dermatitis-like skin lesions reduced by topical application and intraperitoneal injection of Hirsutenone in NC/Nga mice.

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD.

Effect of taxifolin glycoside on atopic dermatitis-like skin lesions in NC/Nga mice.

Increased levels of eosinphils, IgE, IL-4, 5, and 13 and pro-inflammatory factors (COX-2, iNOS) are observed in patients with atopic dermatitis (AD). Taxifolin 3-O-beta-D-glucopyranoside (TAX) from the roots of Rhododendron mucronulatum (RM) was examined to determine whether its immunomodulatory effect was applicable for treating atopic dermatitis.A total of 7 groups of NC/Nga mice with AD were treated by topical application or intraperitoneal injection of TAX for 4 weeks. Follow-up evaluations were done to assess the changes in clinical observations, eosinophil counts, and levels of IgE, cytokines, COX-2 and iNOS.In the clinical observation during the experimental period, TAX treatment significantly reduced the severity of AD-like lesions induced in NC/Nga mice. Eosinophil and IgE levels decreased after treatment of the animals with TAX. TAX may thus be associated with improvement of eosinophil-related allergic diseases. The expression of cytokines (IL-4, 5 and 13) was significantly inhibited in the TAX-treated group, suggesting that TAX might play an immunoregulatory role associated with AD. In RT-PCR, iNOS and COX-2 expression levels were reduced in the TAX-treated group. In western blotting, the expression levels of iNOS and COX-2 were also reduced in the TAX-treated group.These findings suggest that TAX is effective for the treatment of AD by preventing the production of inflammatory cytokines and by reducing skin inflammation.

The anti-oxidative and anti-inflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R. RAYMOND.

Activity guided fractionation of Aconitum koreanum root extract (RAK), a traditional medicine in Korea, afforded four caffeoyl derivatives, caffeic acid (1), 4,5-dicaffeoylquinic acid (2), 3,5-dicaffeoylquinic acid (3) and 3,5-dicaffeoylquinic acid methyl ester (4). In order to evaluate the anti-oxidative and anti-inflammatory effects of these compounds, their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and abilities to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 were examined. And the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated HaCaT cells were also quantified by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Compounds (1-4) showed potent DPPH radical scavenging and NO inhibitory activities as compared with positive controls (L-ascorbic acid and N(G)-monomethyl-L-arginine (L-NMMA), respectively). Also, these compounds dose-dependently inhibited the expressions of iNOS and COX-2 as well as their mRNA levels.

The effect of calcipotriol on the expression of human beta defensin-2 and LL-37 in cultured human keratinocytes.

BACKGROUND: Vitamin D has been reported to regulate innate immunity by controlling the expression of antimicrobial peptides (AMPs). OBJECTIVE: We investigated the effect of calcipotriol on the expression of AMPs in human cultured keratinocytes. METHODS: Keratinocytes were treated with lipopolysaccharide (LPS), TNF-alpha, Calcipotriol and irradiated with UVB, cultured, and harvested. To assess the expression of human beta defensin-2 and LL-37 in the control group, not exposed to any stimulants, the experimental group was treated with LPS, TNF-alpha, or UVB, and another group was treated again with calcipotriol; reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical staining were performed. RESULTS: In the experimental group treated with LPS, UVB irradiation, and TNF-alpha, the expression of beta-defensin and LL-37 was increased more than in the control group and then decreased in the experimental group treated with calcipotriol. CONCLUSIONS: Calcipotriol suppressed HBD-2 and LL-37, which were stimulated by UVB, LPS, and TNF-alpha.

Expression and modulation of LL-37 in normal human keratinocytes, HaCaT cells, and inflammatory skin diseases.

Defensins and cathelicidins (LL-37) are major antimicrobial peptides (AMPs) of the innate immune system of the human skin. In normal non-inflamed skin these peptides are negligible, but their expression can be markedly increased in inflammatory skin disease such as psoriasis. We designed this study to identify the expressions of LL-37 in normal human keratinocyte (NHK) and HaCaT cells after exposure to stimulants and to investigate difference of LL-37 expression accompanied with cell differentiation status, and come to understand difference of susceptibility to infection in atopic dermatitis and psoriasis. Expressions of LL-37 in NHKs and HaCaT cells were evaluated by using RT-PCR, Western blotting, and immunohistochemical (IHC) staining at 6, 12, and 24 hr post stimulation after exposure to Ultraviolet B irradiation and lipopolysaccharide. And expression of LL-37 in skin biopsy specimens from patients with atopic dermatitis and psoriasis was determined by immunohistochemical analysis. In time-sequential analyses of LL-37 expression revealed that LL-37 was expressed in NHKs, but not in HaCaT cells. IHC analysis confirmed the presence of abundant LL-37 in the epidermis of psoriasis. Therefore we deduced that expression of LL-37 is affected by UV irradiation, bacterial infection, and status of cell differentiation.