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The impact of the COVID-19 pandemic on biologic treatment for psoriasis in Japan remains to be elucidated. This study aimed to investigate changes in biologic treatment and patients' behavior of visiting our department, especially in psoriasis patients treated with biologics before and during the pandemic. Data were collected from medical records retrospectively. The numbers of new psoriasis patients before (2019) and during (2020) the pandemic were compared. Patients' behavior of visiting our department was evaluated. The number of new psoriasis patients who visited our department in 2020 decreased by 35.7% compared with that in 2019. The reduction rate of new patients with psoriasis vulgaris was 49.3%, whereas the numbers of new patients with psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP) were almost the same in 2019 and 2020. The number of patients who newly initiated biologics did not decrease in 2020 compared with that in 2019. As of January 1, 2020, 215 psoriasis patients were treated with biologics. Six patients (2.8%) discontinued biologics treatment possibly due to COVID-19 in 2020. Among 212 patients with good adherence to visiting our department in the previous year, 24 patients (11.3%) refrained from their visits for at least 1 month. In most cases, refrainment was observed in April and May when the first state of emergency was in effect in Japan. In conclusion, the COVID-19 pandemic hindered patients from visiting our department. However, its impact on patients who needed intensive care, such as patients with PsA and GPP, and psoriasis patients treated with biologics, was limited.

Dupilumab demonstrated high efficacy and tolerable safety profiles in moderate‐to‐severe atopic dermatitis (AD) patients in clinical trials; however, certain patients suffer from facial redness, while obtaining good responses on the trunk and limbs to dupilumab in the real‐world setting. In our study, we investigated the effectiveness of tacrolimus ointment on facial lesions refractory to topical corticosteroid in patients with AD receiving dupilumab. This study included Japanese adult patients with moderate‐to‐severe AD who developed facial lesions during dupilumab treatment and whose facial lesions became refractory to topical corticosteroid treatment. Nine patients (one female, eight males) were included in this study. One patient newly developed facial erythema after initiating dupilumab. Facial lesions were refractory to dupilumab treatment in the other patients. Five of the nine patients showed improvement in EASI scores of head and neck by switching the facial treatment from topical corticosteroid to tacrolimus ointment. The patient who developed newly facial erythema showed improvement after applying tacrolimus ointment. Although we explored the predictors of effectiveness of tacrolimus ointment in patients with facial lesions during dupilumab treatment, no significant differences were observed in age, duration of dupilumab prior treatment, or prior head and neck EASI between patients who showed improvement after changing to tacrolimus and those who did not. Tacrolimus ointment is worth trying if facial lesions are refractory to topical corticosteroid.

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in the cranial nerve or dorsal root ganglia, with spread of the virus along the sensory nerve to the dermatome. Postherpetic neuralgia is a feared complication of HZ and impairs patients' quality of life enormously. However, there is no predictor of the duration of neuralgia. Our objective was to investigate whether there are correlations between the duration of neuralgia and serum levels of potential biomarkers in order to find practical predictors of the duration of neuralgia. Patients who were diagnosed with HZ at our hospital from April 2013 to January 2014 were included in this study. Serum levels of cytokines and other biomarkers were measured using commercial enzyme-linked immunosorbent assay kits. Thirty patients (15 men and 15 women) with HZ were enrolled in this study. The mean age was 66.1 ± 9.2 (standard deviation) years (range, 51-84 years). Four patients were evaluated as having mild, 19 as having moderate, and seven as having severe HZ. Patients with severe HZ suffered from neuralgia for a significantly longer period of time than patients with mild-to-moderate HZ (9.86 ± 8.25 months vs. 2.01 ± 2.68 months, severe vs. mild-to-moderate, p = 0.0021). The serum interleukin (IL)-10 level was significantly higher in patients with severe HZ than in those with mild-to-moderate HZ (12.93 ± 3.27 pg/mL vs. 6.74 ± 3.72 pg/mL; severe vs. mild-to-moderate; p = 0.0487). Furthermore, the serum IL-10 level was significantly correlated with the duration of neuralgia (r = 0.5193, p = 0.0111). Lastly, the serum IL-10 level significantly decreased after treatment in comparison with that before treatment (from 8.15 ± 4.46 pg/mL to 4.32 ± 11.83 pg/mL, p < 0.0001). In conclusion, these results suggest that the serum IL-10 level is an objective biomarker of the severity of HZ, and that the serum IL-10 level can be a practical predictor of the duration of neuralgia.

Thymus and activation-regulated chemokine (TARC) is designated as a T-helper 2-type chemokine and its expression is upregulated in patients with atopic dermatitis. Previous studies reported that serum TARC levels in patients with psoriasis vulgaris (PsV) were comparable with those in healthy controls. However, the association of clinical severity of psoriasis with serum TARC levels and serum TARC levels in patients with psoriatic arthritis (PsA) or generalized pustular psoriasis (GPP) have never been reported. We investigated the association of serum TARC level with psoriasis by the type of psoriasis, and examine correlations of serum TARC levels with clinical severity scores and other results of blood tests. Data on 75 patients (51 men and 24 women; PsV, 30 patients; PsA, 29 patients; GPP, 16 patients) were analyzed. The serum TARC level was significantly higher in patients with GPP than in patients with PsV and patients with PsA. There was a positive correlation between serum TARC level and Psoriasis Area and Severity Index score (r = 0.3499, P = 0.0030). The serum TARC levels decreased after treatment in GPP patients. Our study revealed that the serum TARC level can potentially be one of the biomarkers reflecting the severity or systemic inflammation caused by psoriasis in patients with psoriasis, although not as much as in patients with atopic dermatitis. Furthermore, serum TARC levels were high in patients with GPP. Those were decreased by treatment, suggesting that serum TARC levels could be utilized as an objective biomarker to evaluate a therapeutic effect in individual GPP patients. Further accumulation of cases and further research are needed to elucidate the role of TARC in psoriasis.

Background The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real-time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. Objective Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non-invasively before operation. Methods We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B-mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty-one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. Results In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. Conclusion Real-time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC.

The combination of BRAF inhibitor and MEK inhibitor is one of the first-line treatments for unresectable BRAF-mutant melanoma or as an adjuvant therapy. However, some patients who received the combination of dabrafenib and trametinib (CombiDT) or the combination of encorafenib and binimetinib (CombiEB) had adverse events (AEs) including pyrexia. We herein report a patient with BRAF-mutated melanoma who repeatedly developed elevated levels of D-dimer and pyrexia after CombiDT and CombiEB treatments. Moreover, concomitant edoxaban prevented these AEs, enabling the patient to continue receiving CombiEB.

Background Psoriasis is a chronic inflammatory skin disease. Anti-TNFα, IL-17A and IL-23p19 antibodies are effective for psoriasis. However, the contribution of regulatory T cells (Treg) in their effectiveness remains to be elucidated. Objective We investigated the effects of TNFα, IL-17A and IL-23p19 inhibition on Tregs in imiquimod-induced psoriasiform dermatitis. Methods Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Mice were treated with anti-TNFα, IL-17A or IL-23p19 monoclonal antibodies every other day from one day before imiquimod application. Results Administration of anti-TNFα, IL-17A or IL-23p19 antibodies improved the clinical score and downregulated Th17-related cytokines and chemokines, while IL-23p19 antibodies upregulated IL-10 mRNA expression. Anti-IL-17A or IL-23p19 antibody-treated imiquimod-applied mice showed a significant increase in the number of Foxp3+ IL-10+ Tregs. Recipient mice adoptively transferred with Tregs derived from donor mice treated with antibodies demonstrated clinical and pathological improvement in imiquimod-induced psoriasiform dermatitis. Anti-IL-17A or IL-23p19 antibody-induced Tregs significantly increased the number of Foxp3+ cells and IL-10 expression in imiquimod-induced psoriasiform dermatitis in recipient mice but anti-TNFα antibody-induced Tregs did not. Conclusion Anti-IL-17A or IL-23p19 antibody inhibits the IL-17/IL-23 signaling pathway, and induces expansion of Tregs and their suppressive capacity in imiquimod-induced psoriasiform dermatitis.

Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12 months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients' charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12 months after initiating dupilumab but not at 1 month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6 months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1 month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases.

Rhododendrol (RD), 4‐(4‐hydroxyphenyl)‐2‐butanol, inhibits melanin synthesis and had been used in skin‐whitening cosmetic products until 2013. However, some individuals developed leukoderma on the skin where RD had been applied and have suffered from refractory depigmentation even after discontinuing RD application. Bimatoprost is a prostaglandin F2α analog and is often used for eyelash growth for cosmetic reasons as well as in the treatment of glaucoma. It was reported that bimatoprost induced skin pigmentation in addition to iris pigmentation as adverse effects. Therefore, we conducted an open‐label single‐center pilot study to evaluate the effectiveness of bimatoprost on refractory RD‐induced leukoderma. Eleven Japanese female patients with skin type III who developed leukoderma on the exact or slightly extended area of skin where RD had been applied and gained a halt of enlargement of leukoderma or repigmentation on a part of the affected skin after discontinuation of RD were enrolled. Bimatoprost 0.03% solution was applied on the leukoderma once daily for 3 months, and then the frequency of application was increased to twice daily for the subsequent 3 months. Ten patients completed the 6‐month course of bimatoprost application. In four patients, bimatoprost application brought slight improvement in RD‐induced refractory leukoderma by dermatologists’ evaluation. Because the number of enrolled patients was limited, further larger studies are necessary to better assess the effectiveness of bimatoprost in inducing repigmentation in patients with RD‐induced refractory leukoderma.

Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti-BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor-related BP than in patients with non-DPP4 inhibitor-related BP. Our results showed that DPP-4 inhibitor-related BP has some distinct pathological characteristics from BP not associated with DPP-4 inhibitor.

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that presents with erythema and sterile pustules, pathologically characterized by Kogoj's spongiform pustules. GPP is sometimes accompanied by mucosal involvement, and the most common lesion is on the tongue. IL36RN mutation was found to contribute to the pathogenesis of GPP especially in patients who develop GPP without a past medical history of psoriasis vulgaris. The association of IL36RN mutation with mucosal involvement in GPP is controversial. We herein report a 60-year-old male GPP patient with no past history of plaque psoriasis presenting with not only severe skin lesions and arthritis but also severe mucosal involvements of pharyngeal and gastrointestinal lesions, which led to gastrointestinal bleeding. Our case did not have any mutation in the IL36RN gene. We should be aware that severe GPP can cause gastrointestinal bleeding. The relevancy of IL36RN mutation with mucosal involvement in GPP remains to be elucidated.

summary Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with baseline serum levels of IgE and TARC but not subjective severity scores in a real-world setting. These objective parameters are useful as practical predictors of later development of conjunctivitis.

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C-reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = -0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis.

Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatitis that is commonly treated with topical corticosteroids and vitamin D3 analogs. The combination of a topical corticosteroid and vitamin D3 analog showed superior efficacy to each alone in clinical trials; however, the mechanisms by which the topical corticosteroid and vitamin D3 analog exert their effects on lesional skin in combination and each alone remain unknown. In this study, we examined the effects of combined calcipotriol (Cal)/betamethasone dipropionate (BD) ointment on psoriasis in vivo, utilizing imiquimod (IMQ)-induced murine psoriasiform skin inflammation, compared with each alone. Vehicle, Cal/BD, Cal or BD was applied on the shaved back skin for 3 consecutive days. Then, IMQ was applied for 6 consecutive days. Twenty-four hours after the last IMQ treatment, the murine skin was evaluated clinically and pathologically. mRNA expressions were examined by quantitative polymerase chain reaction. All ointments alleviated IMQ-induced psoriasiform skin inflammation clinically in comparison with vehicle application. Cal/BD suppressed mRNA expressions of cytokines involved in psoriasis pathogenesis such as interleukin (IL)-17A and IL-22 efficiently. Cal alone induced IL-10 expression, whereas BD alone reduced IL-6 mRNA expression and the number of phosphorylated signal transducer and activator of transcription 3-positive cells in lesional skin. Our study revealed that Cal and BD have different effects on IMQ-induced psoriasiform skin. Some of the immune effects of Cal and BD may be additive or synergistic, which may account for the superior clinical efficacy of their combination.

is missing (Short communication)

The antimicrobial peptide human β-defensin-3 (hBD-3) is produced by epidermal keratinocytes, and exhibits broad killing activity against bacteria or fungi. Prostaglandin D(2) enhances hBD-3 production in human keratinocytes by stimulating a transcription factor, activator protein-1 via chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2). Prostaglandin H(2), a precursor of prostaglandin D(2) can be converted to thromboxane A(2). Certain antimycotic drugs act on keratinocytes and modulate their production of chemokines. In this in vitro study, we examined the effects of antimycotics on hBD-3 production in human keratinocytes. Antimycotics itraconazole and terbinafine hydrochloride increased hBD-3 secretion and mRNA levels in parallel to the enhanced activity of activator protein-1, expression and phosphorylation of activator protein-1 component, c-Fos, but fluconazole was ineffective. These effects were abrogated by CRTH2 antagonist. Itraconazole and terbinafine hydrochloride increased prostaglandin D(2) release from keratinocytes and reduced the release of thromboxane B(2), a thromboxane A(2) metabolite. The conditioned medium from itraconazole or terbinafine hydrochloride-treated keratinocytes inhibited the growth of Candida albicans dependently on hBD-3. These results suggest that itraconazole and terbinafine hydrochloride may enhance c-Fos expression and phosphorylation, activator protein-1 activity and hBD-3 production by increasing prostaglandin D(2) release from keratinocytes. These antimycotic drugs may suppress thromboxane A(2) synthesis and redirect the conversion of prostaglandin H(2) towards prostaglandin D(2). The induction of hBD-3 in keratinocytes is another possible mechanism for the antimycrobial effects of these drugs, which may augment the cutaneous defense activity against infection.

Expression of leucine, leucine-37 (LL-37) is enhanced in keratinocytes of skin lesions with psoriasis. We examined serum LL-37 levels in patients with psoriasis vulgaris. Serum LL-37 levels in patients were higher than in normal controls, and were reduced after cyclosporine A treatment. In both groups, LL-37 and interleukin (IL)-17 levels inversely correlated. In patients, LL-37 levels correlated with interferon (IFN)-γ and IL-10 levels. In controls, LL-37 levels inversely correlated with tumor necrosis factor (TNF)-α, IL-6, IL-1β, and IL-22 levels. IFN-γ, IL-17, IL-22, TNF-α, IL-6, and IL-1β enhanced, and IL-10, IL-4, IL-13, and cyclosporine A suppressed, LL-37 secretion from keratinocytes and neutrophils. LL-37 enhanced IFN-γ, IL-4, IL-13, and TNF-α secretion from CD3/CD28-stimulated T cells, suppressed TNF-α, IL-1β, IL-6, and IL-10 secretion from lipopolysaccharide-stimulated monocytes, and IL-17, IL-22, IL-1β, IL-6, and IL-10 secretion from CD3/CD28-stimulated T cells. LL-37 may sustain its production by enhancing IFN-γ or reducing IL-10 production, while suppressing its production by reducing IL-17, IL-22, TNF-α, IL-1β, or IL-6 and enhancing IL-4 or IL-13 production. In patients, systemic LL-37 production is enhanced, and an IFN-γ/LL-37-positive feedback loop may exist. In controls, negative feedback by LL-37 on TNF-α, IL-1β, IL-22, and IL-6 may exist. In both groups, negative feedback by LL-37 on IL-17 may exist. LL-37 may act as an effector and regulator.

Psoriasis is an inflammatory dermatosis with enhanced expression of hBD-2 in keratinocytes and infiltration of cytokine-producing T cells, which in turn, up- or down-regulate hBD-2 expression. We determined the serum levels of hBD-2 and cytokines in psoriasis patients and analyzed the effects of hBD-2 on cytokine production in human peripheral blood T cells. Serum hBD-2 levels in patients were higher than those in controls and correlated with PASI, serum IFN-γ, and IL-10 levels and correlated inversely with serum IL-17 levels. IFN-γ, IL-17, IL-22, TNF-α, IL-1β, and IL-6 enhanced, and IL-10, IL-4, and IL-13 suppressed hBD-2 secretion from keratinocytes. hBD-2 enhanced secretion and mRNA levels of IFN-γ, TNF-α, IL-10, IL-1β, IL-6, and IL-22 and reduced those of IL-17 in CD3/28-stimulated T cells. These effects of hBD-2 were counteracted by PTX. hBD-2 induced phosphorylation of JNK, ERK, and Akt in T cells. Inhibitors of these signals attenuated hBD-2-induced production of IFN-γ, TNF-α, IL-10, IL-1β, IL-6, and IL-22. hBD-2 suppressed phosphorylation of STAT3 and enhanced expression of SOCS3 in CD3/28-stimulated T cells. siRNA against SOCS3 reversed hBD-2-induced suppression of IL-17 production and STAT3 phosphorylation. JNK and MEK inhibitors suppressed hBD-2-induced expression of SOCS3. In conclusion, hBD-2 may bind PTX-sensitive GPCR(s) on T cells and act as a stimulator by enhancing IFN-γ, TNF-α, IL-1β, IL-6, and IL-22 production via JNK, MEK/ERK, and PI3K/Akt and as a regulator by suppressing IL-17 production via SOCS3 or by stimulating IL-10 production.

The antimicrobial peptide human beta-defensin-3 (hBD-3) is produced by epidermal keratinocytes and protects the skin from infections. This peptide induces the release of a lipid mediator, prostaglandin D(2) from dermal mast cells. Prostaglandin D(2) binds to cell-surface G protein-coupled receptors, D prostanoid receptor, and chemoattractant receptor-homologous molecule expressed on T helper cell type 2 (CRTH2). Both receptors are detected on epidermal keratinocytes. It is reported that prostaglandin D(2) is involved in cutaneous allergy, however, its role in antimicrobial defense is unknown. We examined the in vitro effects of prostaglandin D(2) on hBD-3 production in normal human keratinocytes. Prostaglandin D(2) enhanced hBD-3 secretion and mRNA expression in human keratinocytes. Prostaglandin D(2)-induced hBD-3 production was suppressed by the CRTH2 antagonist ramatroban and by antisense oligonucleotides against c-Jun and c-Fos, components of a transcription factor, activator protein-1 (AP-1). Prostaglandin D(2) enhanced the transcriptional activity and DNA binding of AP-1, expression, phosphorylation, and DNA binding of c-Fos proteins in keratinocytes. Prostaglandin D(2)-induced hBD-3 production, AP-1 activity, and c-Fos expression and phosphorylation were suppressed by U0126, PP2, and pertussis toxin, which are inhibitors of mitogen-activated protein kinase kinase (MEK), src, and G(i) proteins, respectively. The phosphorylation of extracellular signal-regulated kinase (ERK), downstream kinase of MEK, was induced by prostaglandin D(2), and suppressed by ramatroban, pertussis toxin, PP2, and U0126. These results suggest that prostaglandin D(2) induces hBD-3 production in human keratinocytes by activating AP-1 through the expression and phosphorylation of c-Fos via the CRTH2/G(i)/src/MEK/ERK pathway. Prostaglandin D(2) may promote cutaneous antimicrobial activity via hBD-3.