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1.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638865

RESUMO

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives-methylparaben and phenoxyethanol-but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34411589

RESUMO

BACKGROUND: Mechanical alloknesis (or innocuous mechanical stimuli-evoked itch) often occurs in dry skin-based disorders such as atopic dermatitis and psoriasis. However, the molecular and cellular mechanisms underlying mechanical alloknesis remain unclear. We recently reported the involvement of CD26 in the regulation of psoriatic itch. This molecule exhibits dipeptidyl peptidase IV (DPPIV) enzyme activity and exerts its biologic effects by processing various substances, including neuropeptides. OBJECTIVE: The aim of the present study was to investigate the peripheral mechanisms of mechanical alloknesis by using CD26/DPPIV knockout (CD26KO) mice. METHODS: We applied innocuous mechanical stimuli to CD26KO or wild-type mice. The total number of scratching responses was counted as the alloknesis score. Immunohistochemical and behavioral pharmacologic analyses were then performed to examine the physiologic activities of CD26/DPPIV or endomorphins (EMs), endogenous agonists of µ-opioid receptors. RESULTS: Mechanical alloknesis was more frequent in CD26KO mice than in wild-type mice. The alloknesis score in CD26KO mice was significantly reduced by the intradermal administration of recombinant DPPIV or naloxone methiodide, a peripheral µ-opioid receptor antagonist, but not by that of mutant DPPIV without enzyme activity. EMs (EM-1 and EM-2), selective ligands for µ-opioid receptors, are substrates for DPPIV. Immunohistochemically, EMs were located in keratinocytes, fibroblasts, and peripheral sensory nerves. Behavioral analyses revealed that EMs preferentially provoked mechanical alloknesis over chemical itch. DPPIV-digested forms of EMs did not induce mechanical alloknesis. CONCLUSION: The present results suggest that EMs induce mechanical alloknesis at the periphery under the enzymatic control of CD26/DPPIV.

3.
Biochem Biophys Res Commun ; 569: 86-92, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34237432

RESUMO

Neutrophils undergo spontaneous apoptosis within 24-48 h after leaving bone marrow. Apoptotic neutrophils are subsequently phagocytosed and cleared by macrophages, thereby maintaining neutrophil homeostasis. Previous studies have demonstrated involvement of lysophosphatidylglucoside (lysoPtdGlc), a degradation product of PtdGlc, in modality-specific repulsive guidance of spinal sensory axons, via its specific receptor GPR55. In the present study, using human monocytic cell line THP-1 as a model, we demonstrated that lysoPtdGlc induces monocyte/macrophage migration with typical bell-haped curve and a peak at concentration 10-9 M. Lysophosphatidylinositol (lysoPtdIns), a known GPR55 ligand, induced migration at higher concentration (10-7 M). LysoPtdGlc-treated cells had a polarized shape, whereas lysoPtdIns-treated cells had a spherical shape. In EZ-TAXIScan (chemotaxis) assay, lysoPtdGlc induced chemotactic migration activity of THP-1 cells, while lysoPtdIns induced random migration activity. GPR55 antagonist ML193 inhibited lysoPtdGlc-induced THP-1 cell migration, whereas lysoPtdIns-induced migration was inhibited by CB2-receptor inverse agonist. SiRNA experiments showed that GPR55 mediated lysoPtdGlc-induced migration, while lysoPtdIns-induced migration was mediated by CB2 receptor. Our findings, taken together, suggest that lysoPtdGlc functions as a chemotactic molecule for human monocytes/macrophages via GPR55 receptor, while lysoPtdIns induces random migration activity via CB2 receptor.

4.
J Dermatol ; 48(9): e399-e413, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34288036

RESUMO

The mechanisms underlying itch are not fully understood. Physicians usually encounter difficulty controlling itch in generalized pruritus. Since only a small percentage of patients with generalized pruritus respond to antihistamines (H1 receptor antagonists), a variety of itch mediators and mechanisms other than histaminergic signals are considered to be involved in itch for these non-responsive patients. In 2012, we created guidelines for generalized pruritus. Those guidelines have been updated and revised to make some of the definitions, diagnostic terms, and classifications more applicable to daily clinical practice. Cutaneous pruritus as designated in these guidelines is a disease characterized by itch without an observable rash. Generalized pruritus (without skin inflammation) is defined as the presence of itch over a wide area, and not localized to a specific part of the body. This entity includes idiopathic pruritus, pruritus in the elderly, symptomatic pruritus, pregnancy-associated pruritus, drug-induced pruritus, and psychogenic pruritus. Localized pruritus (without skin inflammation) represents fixed itch localized to a specific part of the body, and includes anogenital pruritus, scalp pruritus, notalgia paresthetica, and brachioradial pruritus. These guidelines outline the current concepts and specify the diagnostic methods/treatments for cutaneous pruritus.


Assuntos
Prurido , Dermatopatias , Idoso , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Prurido/diagnóstico , Prurido/tratamento farmacológico , Transtornos Psicofisiológicos
5.
J Dermatol ; 48(9): e414-e431, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34314056

RESUMO

Prurigo is a treatment-resistant skin disease characterized by multiple isolated papules/nodules that cause severe itch. Prurigo papules/nodules occur either as primary lesions or as secondary lesions due to persistent scratching. The fundamental concepts and classifications of prurigo have not been sufficiently established, and considerable confusion remains regarding this topic. Clinical guidelines for chronic prurigo in Japan were published in 2012 in an attempt to reduce confusion regarding the concepts of prurigo and to standardize laboratory tests and treatments. However, the diagnostic terms for prurigo and associated concepts have changed over time, and new forms of treatment are under development. We have, thus, updated and revised the guidelines to classify prurigo based on clinical forms and causes, and disease name classifications based on the clinical form have been further simplified, such as prurigo nodularis, prurigo chronica multiformis, and prurigo (not otherwise specified). Expressions for acute, subacute, and chronic forms are not used. These guidelines outline the current concepts and specify treatments for prurigo.


Assuntos
Prurigo , Administração Tópica , Doença Crônica , Humanos , Prurigo/tratamento farmacológico , Prurigo/terapia , Prurido , Pele
6.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299063

RESUMO

Regulatory T cells (Tregs) suppress immune responses and maintain immunological self-tolerance and homeostasis. We currently investigated relationships between skin barrier condition and Treg behavior using skin barrier-disrupted mice. Skin barrier disruption was induced by repeated topical application of 4% sodium dodecyl sulfate (SDS) on mice. The number of CD4+ forkhead box protein P3 (Foxp3)+ Tregs was higher in 4% SDS-treated skins than in controls. This increasing was correlated with the degree of acanthosis. The numbers of interleukin (IL)-10+ and transforming growth factor (TGF)-ß+ Tregs also increased in 4% SDS-treated skins. Localization of IL-33 in keratinocytes shifted from nucleus to cytoplasm after skin barrier disruption. Notably, IL-33 promoted the migration of Tregs in chemotaxis assay. The skin infiltration of Tregs was cancelled in IL-33 neutralizing antibody-treated mice and IL-33 knockout mice. Thus, keratinocyte-derived IL-33 may induce Treg migration into barrier-disrupted skin to control the phase transition between healthy and inflammatory conditions.


Assuntos
Movimento Celular , Quimiotaxia , Dermatite/patologia , Interleucina-33/fisiologia , Pele/patologia , Linfócitos T Reguladores/imunologia , Animais , Dermatite/imunologia , Dermatite/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pele/metabolismo
7.
Acta Derm Venereol ; 101(7): adv00491, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34043019

RESUMO

The aim of this study is to elucidate the relationship between 2 different types of severity-indicating parameters (i.e. between subjective and objective severity-indicating parametersin patients with atopic dermatitis. The disease severity of 55 patients with atopic dermatitis was assessed using 7 subjective parameters indicating severity, including visual analogue scale for itch, Patient-Oriented Eczema Measure, 5-D itch scale, Dermatology Life Quality Index, Eczema Area and Severity Index, body surface area, and Investigator Global Assessment, and 8 objective parameters indicating severity, including eosinophil relative count, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and thymus and activation-regulated chemokine. Five subjective parameters reflecting itch correlated significantly with eosinophil relative count, but not with neutrophil-to-lymphocyte ratio. In contrast, 2 subjective parameters, mainly reflecting the degree of inflammation and area of affected regions, correlated significantly with neutrophil-to-lymphocyte ratio. The eosinophil relative count may correlate with the degree of itch, while the neutrophil-to-lymphocyte ratio may correlate with the degree of inflammation and the area of the affected region. The eosinophil relative count and neutrophil-to-lymphocyte ratio may thus be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis.


Assuntos
Dermatite Atópica , Eczema , Dermatite Atópica/diagnóstico , Eosinófilos , Humanos , Linfócitos , Neutrófilos , Índice de Gravidade de Doença
8.
PLoS One ; 16(4): e0250663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33905439

RESUMO

In a disease-state-dependent manner, the histamine-resistant itch in dry skin-based skin diseases such as atopic dermatitis (AD) and xerosis is mainly due to hyperinnervation in the epidermis. Semaphorin 3A (Sema3A) is a nerve repulsion factor expressed in keratinocytes and it suppresses nerve fiber elongation in the epidermis. Our previous studies have shown that Sema3A ointment inhibits epidermal hyperinnervation and scratching behavior and improves dermatitis scores in AD model mice. Therefore, we consider Sema3A as a key therapeutic target for improving histamine-resistant itch in AD and xerosis. This study was designed to screen a library of herbal plant extracts to discover compounds with potential to induce Sema3A in normal human epidermal keratinocytes (NHEKs) using a reporter gene assay, so that positive samples were found. Among the positive samples, only the extract of S. baicalensis was found to consistently increase Sema3A levels in cultured NHEKs in assays using quantitative real-time PCR and ELISA. In evaluation of reconstituted human epidermis models, the level of Sema3A protein in culture supernatants significantly increased by application of the extract of S. baicalensis. In addition, we investigated which components in the extract of S. baicalensis contributed to Sema3A induction and found that baicalin and baicalein markedly increased the relative luciferase activity, and that baicalein had higher induction activity than baicalin. Thus, these findings suggest that S. baicalensis extract and its compounds, baicalin and baicalein, may be promising candidates for improving histamine-resistant itch via the induction of Sema3A expression in epidermal keratinocytes.


Assuntos
Extratos Vegetais/química , Scutellaria baicalensis/química , Semaforina-3A/metabolismo , Linhagem Celular , Flavanonas/genética , Flavanonas/metabolismo , Flavonoides/genética , Flavonoides/metabolismo , Genes Reporter , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Modelos Biológicos , Extratos Vegetais/farmacologia , RNA Mensageiro/metabolismo , Scutellaria baicalensis/metabolismo , Semaforina-3A/genética
10.
Plast Reconstr Surg Glob Open ; 9(2): e3393, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33680648

RESUMO

Adenoid cystic carcinoma (ACC) is a relatively rare malignant tumor. It is more common in women than in men and typically develops in the lacrimal, salivary, and breast glands. ACC of the external auditory canal (EAC) is exceedingly rare, and its invasion into the ear lobe is even more unusual. In this report, we present a case of ACC that presented as a mass on the surface of the ear lobe in a 28-year-old woman and was initially diagnosed as infected atheroma. For wide resection of the tumor, half of the entire auricula was resected and superficial parotidectomy was performed. After confirming no tumor cells on the surface of the facial nerve, the defect was reconstructed by the combination of platysma muscle flap to prevent Frey syndrome and free forearm flap for the ear lobe form. There was no recurrence or metastasis of the tumor, and Frey syndrome did not occur at 2 years and 8 months after surgery. The patient was satisfied with the result, oncologically and cosmetically. Even in young patients, comprehensive treatments (including diagnosis, resection, and reconstruction) are important in painful ear lobe masses.

11.
Int J Mol Sci ; 21(21)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182442

RESUMO

Itch (or pruritus) was not previously recognized as a serious symptom of psoriasis. However, approximately 60-90% of psoriatic patients with pruritus have stated that it deteriorates their quality of life. Since conventional antipruritic therapies, such as antihistamines, only exert limited effects, the establishment of a treatment option for itch in psoriasis is urgently needed. Although a definitive drug is not currently available, various itch mediators are known to be involved in pruritus in psoriasis. In this review, we describe the clinical features of pruritus in psoriasis, classify a wide range of itch mediators into categories, such as the nervous, immune, endocrine, and vascular systems, and discuss the mechanisms by which these mediators induce or aggravate itch in the pathophysiology of psoriasis.


Assuntos
Prurido/patologia , Psoríase/patologia , Animais , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença
12.
Clin Exp Rheumatol ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32828146

RESUMO

OBJECTIVES: Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro. METHODS: Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin. RESULTS: Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin. CONCLUSIONS: These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.

13.
Biochem Biophys Res Commun ; 529(4): 1073-1079, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32819567

RESUMO

DNA methylation is an epigenetic modification that regulates gene transcription. DNA methyltransferase 1 (DNMT1) plays an important role in DNA methylation. However, the involvement of DNMT1 and DNA methylation in the pathogenesis of atopic dermatitis (AD) remains unclear. In this study, microarray analysis revealed that peripheral blood mononuclear cells of AD patients with low DNMT1 expression (DNMT1-low) highly expressed dendritic cell (DC) activation-related genes. Also, DNMT1-low AD patients exhibited a higher itch score compared to AD patients with high DNMT1 expression (DNMT1-high). By using an AD-like mouse model induced by the application of Dermatophagoides farinae body ointment, we found that Dnmt1 expression was decreased, while the expression of C-C chemokine receptor type 7 (Ccr7) was upregulated in mouse skin DCs. Furthermore, mice exposed to social defeat stress exhibited Dnmt1 downregulation and Ccr7 upregulation in skin DCs. Additionally, dermatitis and itch-related scratching behavior were exacerbated in AD mice exposed to stress. The relationship between low DNMT1 and itch induction was found in both human AD patients and AD mice. In mouse bone marrow-derived DCs, Ccr7 expression was inhibited by 5-aza-2-deoxycytidine, a methylation inhibitor. Furthermore, in mouse skin DCs, methylation of CpG sites in Ccr7 was modified by either AD induction or social defeat stress. Collectively, these findings suggest that social defeat stress exacerbates AD pathology through Dnmt1 downregulation and Ccr7 upregulation in mouse skin DCs. The data also suggest a role of DNMT1 downregulation in the exacerbation of AD pathology.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Células Dendríticas/metabolismo , Dermatite Atópica/enzimologia , Regulação para Baixo , Receptores CCR7/genética , Derrota Social , Estresse Psicológico/enzimologia , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Metilação de DNA , Dermatite Atópica/sangue , Dermatite Atópica/genética , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Prurido/sangue , Prurido/patologia , Receptores CCR7/metabolismo , Pele/patologia , Estresse Psicológico/sangue
15.
Sci Rep ; 10(1): 4360, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152328

RESUMO

Because intractable itch reduces quality of life, understanding the fundamental mechanisms of itch is required to develop antipruritic treatments. Itch is mediated by peripheral sensory neurons, which originate from the neural crest (NC) during development. Itch-associated signaling molecules have been detected in genetically engineered animals and in cultures of peripheral neurons from dorsal root ganglia (DRG). Ethical difficulties collecting peripheral neurons from human DRG have limited analysis of itch in humans. This study describes a method of differentiating peripheral neurons from human induced pluripotent stem cells (hiPSCs) for physiological study of itch. This method resulted in the robust induction of p75 and HNK1 double-positive NC cells from hiPSCs. The expression of NC markers TFAP2A, SOX10 and SNAI1 increased during NC induction. The induction efficiency was nearly 90%, and human peripheral neurons expressing peripherin were efficiently differentiated from hiPSC-derived NC cells. Moreover, induced peripheral neurons expressed the sensory neuronal marker BRN3A and the itch-related receptors HRH1, MRGPRX1, IL31R and IL-4R. Calcium imaging analyses indicated that these peripheral neurons included sensory neurons responsive to itch-related stimuli such as histamine, BAM8-22, IL-31 and IL-4. These findings may enable detailed analyses of human DRG neurons and may result in new therapies for intractable itch.


Assuntos
Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Crista Neural/citologia , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/metabolismo , Apoptose , Biomarcadores , Diferenciação Celular/genética , Células Cultivadas , Imunofluorescência , Humanos , Imunofenotipagem , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Neurogênese
17.
J Dermatol ; 47(4): 413-417, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31985094

RESUMO

Kakato-tsurutsuru (Kt) socks have been selling for almost 30 years in Japan. Wearers claim they improve heel dryness despite no scientific evidence. We investigated the effects of Kt socks on heel dryness by questionnaire, clinical scores and non-invasive skin measurements. In a double-blind, randomized cross-over study, 10 healthy volunteers wore control or Kt socks over 2 weeks in sequence for 4 weeks. Skin hydration and evaporation of the medial and dorsal heel were measured before and every week during the trial. Clinical evaluations of desquamation and cracked skin were scored by a dermatologist. A visual analog scale (VAS) questionnaire of comfort, sock climate humidity and skin dryness was conducted. The VAS of comfort was significantly higher in Kt than controls. Average Δskin dryness in control and Kt groups was -1.63 and 2.22, respectively, showing a significant improvement. In the clinical findings of the dorsal side of the heel, Δdesquamation and Δcracked skin scores were significantly decreased and Δstratum corneum hydration significantly increased in Kt compared with controls. Kt socks may retain evaporated sweat with components of natural moisturizing factors, supporting the water-holding ability of the heel stratum corneum. These findings suggest that Kt socks may improve heel skin dryness.


Assuntos
Vestuário , Emolientes/administração & dosagem , Epiderme/efeitos dos fármacos , Perda Insensível de Água/efeitos dos fármacos , Idoso , Estudos Cross-Over , Método Duplo-Cego , Epiderme/metabolismo , Feminino , Voluntários Saudáveis , Calcanhar , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
J Invest Dermatol ; 140(7): 1346-1354.e5, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31945349

RESUMO

Epidermal keratinocytes are primarily involved in the expression of semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated the signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression is transiently increased in calcium-stimulated NHEKs, whereas it is markedly decreased in terminally differentiated NHEKs. Sema3A mRNA is mainly localized in the stratum basale and stratum suprabasale of the epidermis. We cloned the 5'-flanking region of the Sema3A gene and identified a critical region for Sema3A promoter activity within -134 base pairs of the start codon. We found transcription factor binding sites, including that for activator protein (AP)-1, in this region. Sema3A expression was increased by the co-overexpression of JunB and Fra-2 in the presence of 0.1 or 1.4 mM calcium. The calcium-mediated transient upregulation of Sema3A expression was significantly suppressed by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 or AP-1 inhibitors. These results demonstrate that the calcium-mediated transient upregulation of Sema3A in NHEKs is involved in the MEK/ERK and AP-1 signaling axis. Therefore, Sema3A mRNA may be expressed in the lower epidermis under controlled conditions by calcium via the MAPK-AP-1 axis.


Assuntos
Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Semaforina-3A/metabolismo , Fator de Transcrição AP-1/metabolismo , Sítios de Ligação , Cálcio/metabolismo , Diferenciação Celular , Linhagem Celular , Células Epidérmicas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Humanos , Queratina-10/metabolismo , Queratina-14/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais
19.
Acta Derm Venereol ; 100(2): adv00024, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940044

RESUMO

Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera-peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.


Assuntos
Antipruriginosos/uso terapêutico , Prurido/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Antipruriginosos/efeitos adversos , Humanos , Prurido/diagnóstico , Prurido/etiologia , Prurido/metabolismo , Fatores de Risco , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Resultado do Tratamento , Perda Insensível de Água
20.
Photodermatol Photoimmunol Photomed ; 36(3): 185-191, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31880842

RESUMO

BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.


Assuntos
Dermatite Atópica/microbiologia , Dermatite Atópica/radioterapia , Lasers de Excimer/uso terapêutico , Microbiota/efeitos da radiação , Pele/microbiologia , Adulto , Bacteroidetes/isolamento & purificação , Cianobactérias/isolamento & purificação , Feminino , Humanos , Malassezia/isolamento & purificação , Masculino , Fenômenos Fisiológicos da Pele/efeitos da radiação , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Perda Insensível de Água/efeitos da radiação , Adulto Jovem
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