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BACKGROUND@#The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is critically involved in the pathogenesis of a variety of skin diseases. The aim of this study was to detect AhR and its downstream regulators including cytochrome P450 (CYP1A1), AhR nuclear translocation (ARNT), and aryl hydrocarbon receptor repressor (AhRR) in serum, peripheral blood mononuclear cells (PBMCs), and skin lesions in patients with atopic dermatitis (AD).@*METHODS@#Twenty-nine AD patients defined according to the criteria of Hanifin and Rajka and Chinese criteria of AD were included. Subjects without allergic and chronic diseases were recruited as controls. Patients and controls were selected from the dermatology outpatient clinic of Peking University People's Hospital from August 1 to December 31 in 2018. Enzyme-linked immunosorbent assay was performed to detect serum AhR level. The mRNA of AhR, AhRR, ARNT, and CYP1A1 in PBMCs were measured by real-time quantitative polymerase chain reaction. AhR expression in skin lesions was measured by immunohistochemistry.@*RESULTS@#AhR was significantly higher expressed in serum (41.26 ± 4.52 vs. 33.73 ± 2.49 pmol/L, t = 6.507, P < 0.001) and skin lesions (0.191 ± 0.041 vs. 0.087 ± 0.017, t = 10.036, P < 0.001) of AD patients compared with those of controls. The mRNA levels of AhR (1.572 ± 0.392 vs. 1.000 ± 0.173, t = 6.819, P < 0.001), AhRR (2.402 ± 1.716 vs. 1.000 ± 0.788, t = 3.722, P < 0.001), CYP1A1 (2.258 ± 1.598 vs. 1.000 ± 0.796, t = 3.400, P = 0.002) in PBMCs of AD patients were higher compared with those of controls. The difference in mRNA levels of ARNT was not statistically significant between the patients and controls (1.383 ± 0.842 vs. 1.000 ± 0.586, t = 1.653, P = 0.105). AhR mRNA levels in PBMCs positively correlated with eczema area and severity index score and serum interleukin-6 levels.@*CONCLUSION@#AhR and its downstream regulators were highly expressed in serum, PBMCs, and skin of AD patients, which might contribute to the pathogenesis of AD.
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<p><b>BACKGROUND</b>Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms.</p><p><b>METHODS</b>Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study. Skin biopsy was done in five AD-like GVHD patients, eight LP-like GVHD patients, and eight healthy volunteers. The intensity of pruritus was assessed by visual analog scale itch score and detailed pruritus score. Transepidermal water loss (TEWL) was measured using Tewameter® TM 300. Immunohistochemistry was used to observe the expression of loricrin, involucrin, LL37, and human β-defensins 2 (hBD2) in skin lesions. Western blot analysis was used for analyzing the protein levels of loricrin and involucrin in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of LL37 and hBD2 in skin lesions.</p><p><b>RESULTS</b>Pruritus score was higher in patients with AD-like GVHD (11.33 ± 5.35) than that of patients with LP-like GVHD (2.58 ± 3.09, P< 0.001). Compared with healthy controls (HCs, 4.52 ± 1.24 g·m-2·h-1), TEWL was increased in AD-like GVHD (26.72 ± 9.02 g·m-2·h-1, P < 0.001) and LP-like GVHD patients (18.78 ± 4.57 g·m-2·h-1, P< 0.001), and expressions of loricrin and involucrin were also increased in skin lesions of AD-like GVHD and LP-like GVHD patients (all P< 0.05). LL37 mRNA expression was decreased in lesions of AD-like GVHD and LP-like GVHD patients (P = 0.005 and P = 0.008, vs. HCs, respectively). hBD2 mRNA expression was increased in skin lesions of AD-like GVHD and LP-like GVHD patients (P = 0.002 and P< 0.001, vs. HCs, respectively).</p><p><b>CONCLUSIONS</b>Skin barrier dysfunction is present in AD-like GVHD and LP-like GVHD. The immunoreactions, but not the congenital defect, are considered to be the primary cause of skin barrier impairment in AD-like GVHD and LP-like GVHD.</p>
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<p><b>BACKGROUND</b>Antimicrobial peptides, including cathelicidin LL-37, human beta defensin (HBD)-2, and HBD-3, are important elements of the innate immune response and involved in modulation of the adaptive immunity, and they also play an important role in cutaneous defense against Mycobacterium tuberculosis.</p><p><b>METHODS</b>The fresh skin tissues and paraffin-embedded biopsy samples from three cutaneous tuberculosis, two tuberculids, and ten healthy individuals were collected. The expressions of LL-37, HBD-2, and HBD-3 mRNA in the lesions of three cutaneous tuberculosis and two tuberculids were detected by quantitative real-time polymerase chain reaction; the protein expressions were detected by immunohistochemistry and Western blotting methods.</p><p><b>RESULTS</b>The expressions of LL-37 mRNA and protein in the lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. The expression of HBD-2 mRNA had an increasing trend in the lesions of cutaneous tuberculosis and tuberculids compared with that of normal skin; however, the expression of HBD-2 protein in the lesions of cutaneous tuberculosis had a decreasing trend compared with that of normal skin, and the expression of HBD-2 protein in the lesions of tuberculids was similar to that of normal skin. The expressions of HBD-3 mRNA and protein in lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin.</p><p><b>CONCLUSIONS</b>Our study indicated that the expression of HBD-2 and HBD-3 mRNA and protein in lesions of cutaneous tuberculosis may be not consistent with that of tuberculids. However, an inherent limitation of the present study was that the sample size was small, and the roles and regulation mechanisms of LL-37, HBD-2, and HBD-3 in cutaneous tuberculosis and tuberculids need to be further investigated.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antimicrobial Cationic Peptides , Genetics , RNA, Messenger , Tuberculosis, Cutaneous , Metabolism , beta-Defensins , GeneticsABSTRACT
<p><b>BACKGROUND</b>Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.</p><p><b>METHODS</b>A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.</p><p><b>RESULTS</b>A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.</p><p><b>CONCLUSION</b>Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Dermatitis, Atopic , Diagnosis , Allergy and Immunology , Eczema , Diagnosis , Immunoglobulin E , Blood , Retrospective Studies , Surveys and QuestionnairesABSTRACT
<p><b>BACKGROUND</b>Tetracycline (TET) has been found to have both antibiotic and anti-inflammatory properties. The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported. The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD.</p><p><b>METHODS</b>The 2% TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day. AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis, ear thickness, and frequency of scratching. Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay. Western blot was used for analyzing the expressions of TSLP, protease-activated receptor 2 (PAR2), and nuclear factor-kappa B (NF-κB) in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, and IL-1β in skin lesions.</p><p><b>RESULTS</b>Scoring of dermatitis (9.00 ± 0.63 vs. 6.67 ± 1.03, P = 0.001), ear thickness (0.44 ± 0.02 mm vs. 0.40 ± 0.03 mm, P = 0.018), and serum IgE level (421.06 ± 212.13 pg/ml vs. 244.15 ± 121.39 pg/ml, P = 0.047) were all improved in the 2% TET treatment group compared with AD group. Topical TET significantly reduced the serum level of TSLP (119.04 ± 38.92 pg/ml vs. 65.95 ± 54.61 pg/ml, P = 0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P = 0.003 and 0.011, respectively), and NF-κB and PAR2 expression in skin lesions were also suppressed (P = 0.016 and 0.040, respectively). Furthermore, expressions of inflammatory cytokines IL-4, IL-13, and TNF-α in skin lesions were down-regulated in 2% TET group compared with AD group (P = 0.035, 0.008, and 0.044, respectively).</p><p><b>CONCLUSIONS</b>Topical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model, suggesting TET as a potential agent for the topical treatment of AD in the future.</p>