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1.
Dermatol Online J ; 26(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621682

RESUMO

A striking dermatitis referred to by its colloquial designation of sabra dermatitis is associated with glochidia inoculation from the Opuntia cactus commonly known as the prickly pear. We report a 45-year-old woman who had an unexpected encounter with a cactus plant during a trip to Texas. She brushed up against the plant and was aware that she had been inoculated with several spines of the plant. Five days later she developed erythematous papules on the digits accompanied by swelling. The biopsy showed a very striking granulomatous reaction pattern within the dermis. There was a linear pattern of necrobiosis, likely representing a tract of inoculation injury palisaded by histiocytes including multinucleated forms. This necrobiotic tract demonstrated retained glochidia, each measuring roughly 40 to 70 microns in diameter. The nature of the inflammatory response is one that combines features of classic delayed hypersensitivity and an innate foreign body response. The glochidia are capable of eliciting a T cell mediated immune response; it is reasonable to assume that a Th1 cytokine signal is responsible for the unique pattern of inflammation including the secondary influx of neutrophils and relative lack of tissue eosinophilia.


Assuntos
Dermatite/etiologia , Hipersensibilidade Tardia/etiologia , Opuntia/efeitos adversos , Dermatite/imunologia , Dermatite/patologia , Feminino , Humanos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/patologia , Pessoa de Meia-Idade
2.
Parasite Immunol ; 42(6): e12710, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32145079

RESUMO

Trichobilharzia regenti (Schistosomatidae) percutaneously infects birds and mammals and invades their central nervous system (CNS). Here, we characterized the peripheral immune response of infected mice and showed how it was influenced by the parasite-induced inflammation in the skin and the CNS. As revealed by flow cytometry, T cells expanded in the spleen and the CNS-draining lymph nodes 7-14 days post-infection. Both T-bet+ and GATA-3+ T cells were markedly elevated suggesting a mixed type 1/2 immune response. However, it dropped after 7 dpi most likely being unaffected by the neuroinflammation. Splenocytes from infected mice produced a high amount of IFN-γ and, to a lesser extent, IL-10, IL-4 and IL-17 after in vitro stimulation by cercarial homogenate. Nevertheless, it had only a limited capacity to alter the maturation status of bone marrow-derived dendritic cells (BMDCs), contrary to the recombinant T. regenti cathepsin B2, which also strongly augmented expression of Ccl5, Cxcl10, Il12a, Il33 and Il10 by BMDCs. Taken together, mice infected with T. regenti developed the mixed type 1/2 immune response, which was driven by the early skin inflammation rather than the late neuroinflammation. Parasite peptidases might play an active role in triggering the host immune response.


Assuntos
Cercárias/imunologia , Dermatite/parasitologia , Schistosomatidae/imunologia , Linfócitos T/imunologia , Infecções por Trematódeos/imunologia , Animais , Catepsina B/metabolismo , Citocinas/imunologia , Células Dendríticas/imunologia , Dermatite/imunologia , Dermatite/patologia , Feminino , Inflamação/parasitologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Pele/imunologia , Pele/parasitologia , Pele/patologia , Infecções por Trematódeos/parasitologia
3.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979308

RESUMO

Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health.


Assuntos
Acne Vulgar/dietoterapia , Dermatite/dietoterapia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/uso terapêutico , Psoríase/dietoterapia , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Acne Vulgar/prevenção & controle , Dermatite/imunologia , Dermatite/metabolismo , Dermatite/prevenção & controle , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Regulação da Expressão Gênica/imunologia , Regulação da Expressão Gênica/fisiologia , Humanos , Psoríase/imunologia , Psoríase/prevenção & controle , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Ácido gama-Linolênico/uso terapêutico
4.
Vet Dermatol ; 31(1): 5-27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957202

RESUMO

BACKGROUND: Demodicosis is a common disease in small animal veterinary practice worldwide with a variety of diagnostic and therapeutic options. OBJECTIVES: To provide consensus recommendations on the diagnosis, prevention and treatment of demodicosis in dogs and cats. METHODS AND MATERIALS: The authors served as a Guideline Panel (GP) and reviewed the literature available before December 2018. The GP prepared a detailed literature review and made recommendations on selected topics. A draft of the document was presented at the North American Veterinary Dermatology Forum in Maui, HI, USA (May 2018) and at the European Veterinary Dermatology Congress in Dubrovnik, Croatia (September 2018) and was made available via the World Wide Web to the member organizations of the World Association for Veterinary Dermatology for a period of three months. Comments were solicited and responses were incorporated into the final document. CONCLUSIONS: In young dogs with generalized demodicosis, genetic and immunological factors seem to play a role in the pathogenesis and affected dogs should not be bred. In old dogs and cats, underlying immunosuppressive conditions contributing to demodicosis should be explored. Deep skin scrapings are the diagnostic gold standard for demodicosis, but trichograms and tape squeeze preparations may also be useful under certain circumstances. Amitraz, macrocyclic lactones and more recently isoxazolines have all demonstrated good efficacy in the treatment of canine demodicosis. Therapeutic selection should be guided by local drug legislation, drug availability and individual case parameters. Evidence for successful treatment of feline demodicosis is strongest for lime sulfur dips and amitraz baths.


Assuntos
Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico , Dermatite/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Infestações por Ácaros/veterinária , Animais , Doenças do Gato/imunologia , Gatos , Dermatite/imunologia , Dermatite/parasitologia , Doenças do Cão/imunologia , Cães , Inseticidas/uso terapêutico , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/imunologia , Ácaros/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/parasitologia , Pele/patologia , Medicina Veterinária/métodos , Medicina Veterinária/organização & administração
5.
J Leukoc Biol ; 107(6): 941-952, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31985117

RESUMO

Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase-dependent apoptosis and caspase-independent necroptosis. The kinase activity of RIP1 has been associated with a number of inflammatory, neurodegenerative, and oncogenic diseases. In this study, we use the RIP1 kinase inhibitor GNE684 to demonstrate that RIP1 inhibition can effectively block skin inflammation and immune cell infiltrates in livers of Sharpin mutant (Cpdm; chronic proliferative dermatitis) mice in an interventional setting, after disease onset. On the other hand, genetic inactivation of RIP1 (RIP1 KD) or ablation of RIP3 (RIP3 KO) or MLKL (MLKL KO) did not affect testicular pathology of aging male mice. Likewise, infection with vaccinia virus or with mouse gammaherpesvirus MHV68 resulted in similar viral clearance in wild-type, RIP1 KD, and RIP3 KO mice. In summary, this study highlights the benefits of inhibiting RIP1 in skin inflammation, as opposed to its lack of relevance for testicular longevity and the response to certain viral infections.


Assuntos
Dermatite/genética , Infecções por Herpesviridae/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Pele/imunologia , Vaccinia/genética , Animais , Doença Crônica , Dermatite/imunologia , Dermatite/patologia , Dermatite/virologia , Modelos Animais de Doenças , Gammaherpesvirinae/imunologia , Gammaherpesvirinae/patogenicidade , Regulação da Expressão Gênica , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Inflamação , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/deficiência , Proteínas Quinases/genética , Proteínas Quinases/imunologia , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Proteína Serina-Treonina Quinases de Interação com Receptores/deficiência , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Transdução de Sinais , Pele/patologia , Pele/virologia , Testículo/imunologia , Testículo/patologia , Testículo/virologia , Vaccinia/imunologia , Vaccinia/patologia , Vaccinia/virologia , Vírus Vaccinia/imunologia , Vírus Vaccinia/patogenicidade , Replicação Viral/imunologia
6.
Vet Dermatol ; 30(6): 517-e157, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31486560

RESUMO

BACKGROUND: Canine acute eosinophilic dermatitis with oedema (CAEDE) and sterile neutrophilic dermatosis have overlapping clinical and histopathological features. HYPOTHESIS/OBJECTIVES: The objective of this study was to identify features that differentiate these entities. ANIMALS: Forty dogs. METHODS AND MATERIALS: Retrospective case series. Forty cases with diagnoses of either CAEDE and/or sterile neutrophilic dermatosis were included based on histopathological review. Medical records (29 of 40 dogs) were reviewed for clinical findings and historical data. Commercially available immunohistochemical stains for granulocytes and a Luna stain were performed (40 of 40 dogs) to assess the granulocytic infiltrate. RESULTS: Nineteen cases had been previously diagnosed as CAEDE, seven cases had been designated as sterile neutrophilic dermatosis and 14 cases had overlapping features. Based on review and receiver operating characteristic (ROC) curve analysis, 30 cases with >12% eosinophils, enumerated by Luna staining, were diagnosed as eosinophilic dermatitis and oedema. Ten cases were diagnosed as sterile neutrophilic dermatosis. Dogs with CAEDE frequently had gastrointestinal signs (24 of 30;80%) and pruritus (11 of 30;33%). In dogs with sterile neutrophilic dermatosis, five of 10 (50%) had diagnoses of or histories compatible with immune-mediated polyarthropathy. CONCLUSIONS AND CLINICAL IMPORTANCE: In this case series, CAEDE was encountered more frequently than neutrophilic dermatosis and could be distinguished by the eosinophilic infiltrate, aided by a Luna stain. Concurrent arthralgia was more frequently identified with neutrophilic dermatosis. It remains unclear whether CAEDE and sterile neutrophilic dermatosis are separate disease entities or varied manifestations of the same disease.


Assuntos
Dermatite/veterinária , Doenças do Cão/diagnóstico , Edema/veterinária , Pele/imunologia , Síndrome de Sweet/veterinária , Animais , Biópsia , Dermatite/diagnóstico , Dermatite/imunologia , Doenças do Cão/imunologia , Cães , Edema/etiologia , Edema/imunologia , Feminino , Masculino , Estudos Retrospectivos , Pele/patologia , Síndrome de Sweet/fisiopatologia
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 595-600, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537243

RESUMO

Objective To observe the effect of esculentoside A (EsA) on Th17 cell-related factors in psoriasis-like mouse model. Methods A total of 48 female BALB/c mice were randomly divided into blank control group, model group, Tuiyin decoction group [66.60 g/(kg.d)], low-, middle- and high-dose groups of EsA [5, 10, 20 mg/(kg.d), respectively], 8 mice in each group. Psoriasis mouse model was induced by imiquimod. Pathological changes of skin lesions in mice were assessed by psoriasis area and severity index (PASI) and HE staining. ELISA was used to detect the changes of interleukin-17 (IL-17), IL-22, IL-6 and tumor necrosis factor-α (TNF-α). Results Compared with the model group, the skin lesions, pathological changes and PASI scores were improved after the treatments with either Tuiyin decoction or EsA, among which the PASI score of Tuiyin decoction group and high-dose group of EsA decreased significantly. The expression of Th17 cell-related factors of the model group was obviously higher than that of the blank control group. Each treated group had obviously lower expression than the model group, and the expression of IL-6 of high-dose group of EsA was close to the blank control group. Conclusion EsA may improve the skin lesions of the psoriasis-like mice by down-regulating the expression of Th17 cell-related cytokines.


Assuntos
Dermatite/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Psoríase/tratamento farmacológico , Saponinas/farmacologia , Células Th17/imunologia , Animais , Citocinas/imunologia , Dermatite/imunologia , Feminino , Imiquimode , Camundongos , Camundongos Endogâmicos BALB C , Ácido Oleanólico/farmacologia , Psoríase/induzido quimicamente , Distribuição Aleatória , Pele/imunologia , Pele/patologia
8.
Int Immunopharmacol ; 75: 105817, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446161

RESUMO

Artesunate (ART), a derivative of artemisinin, is a medication to treat malaria. Beyond that, the anti-inflammatory and immunoregulatory activities of ART have been identified in autoimmune diseases. However, whether ART functions in psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7/8 agonist) is currently unkown. There, we found that the cumulative score, epidermal thickening and expression of Ki-67 of ART-treated BALB/c mice were significantly lower than those in the IMQ psoriatic model group. In addition, ART treatment ameliorated mice from systemic inflammation. Mechanistically, ART reduced γδ T cells in draining lymph nodes, which might be benefit the improvement of dermatitis. These findings suggested that ART could be a promising drug of psoriasis in clinic.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artesunato/uso terapêutico , Dermatite/tratamento farmacológico , Psoríase/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Artesunato/farmacologia , Dermatite/imunologia , Dermatite/patologia , Imiquimode , Linfócitos Intraepiteliais/efeitos dos fármacos , Linfócitos Intraepiteliais/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia
9.
Nat Commun ; 10(1): 3878, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462647

RESUMO

T cell-mediated autoimmunity encompasses diverse immunopathological outcomes; however, the mechanisms underlying this diversity are largely unknown. Dysfunction of the tripartite linear ubiquitin chain assembly complex (LUBAC) is associated with distinct autonomous immune-related diseases. Cpdm mice lacking Sharpin, an accessory subunit of LUBAC, have innate immune cell-predominant dermatitis triggered by death of LUBAC-compromised keratinocytes. Here we show that specific gene ablation of Sharpin in mouse Treg causes phenotypes mimicking cpdm-like inflammation. Mechanistic analyses find that multiple types of programmed cell death triggered by TNF from tissue-oriented T cells initiate proinflammatory responses to implicate innate immune-mediated pathogenesis in this T cell-mediated inflammation. Moreover, additional disruption of the Hoip locus encoding the catalytic subunit of LUBAC converts cpdm-like dermatitis to T cell-predominant autoimmune lesions; however, innate immune-mediated pathogenesis still remains. These findings show that T cell-mediated killing and sequential autoinflammation are common and crucial for pathogenic diversity during T cell-mediated autoimmune responses.


Assuntos
Dermatite/imunologia , Proteínas do Tecido Nervoso/genética , Ubiquitina/metabolismo , Animais , Apoptose , Autoimunidade , Dermatite/patologia , Imunidade Inata , Inflamação/imunologia , Inflamação/patologia , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Linfócitos T , Ubiquitina-Proteína Ligases/metabolismo
10.
Arch Dermatol Res ; 311(9): 705-710, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31350578

RESUMO

Eosinophils are seen in a number of dermatologic conditions. While the extent of their function in these diseases remains to be fully elucidated, pathogenic activity in bullous pemphigoid suggests a more significant role than previously thought. Several dermatoses have a fairly characteristic histologic morphology of eosinophil infiltration. We hypothesized that epidermal expression of eotaxins and TSLP would differ by disease, perhaps explaining the different histologic morphologies. We performed a retrospective study of eosinophil rich dermatoses to perform immunohistochemistry. We collected 49 specimens composed of bullous pemphigoid (n = 15), atopic dermatitis (n = 12), drug rash (n = 8), arthropod assault (n = 5), and non-bullous pemphigoid eosinophilic spongiosis (n = 5). We used lichen planus (n = 4) as a control for lymphocyte-mediated inflammation. TSLP was diffusely expressed in all epidermal samples, whereas eotaxins demonstrated a weaker staining. Eotaxins and TSLP demonstrated a gradient between basal and spinous keratinocytes. The correlation between overall basal keratinocyte and spinous keratinocyte staining of eotaxins and TSLP with the number of eosinophils demonstrated a significant correlation between eotaxin-1 (R = 0.404, P = 0.004), eotaxin-2 (R = 0.576, P < 0.001), and eotaxin-3 (R = 0.512, P < 0.001), but not TSLP (R = 0.164, P = 0.251). These remained significant after correcting for multiple comparisons. While we were unable to detect significant differences in epidermal expression of eotaxins and TSLP in various eosinophil rich dermatoses, we identified a significant correlation of spinous keratinocyte eotaxin staining with tissue eosinophilia. Our identification of a correlation of spinous keratinocyte eotaxin staining with tissue eosinophilia may provide insight into local eosinophil chemotaxis.


Assuntos
Quimiocina CCL11/metabolismo , Quimiocina CCL24/metabolismo , Quimiocina CCL26/metabolismo , Citocinas/metabolismo , Dermatite/patologia , Eosinofilia/patologia , Quimiocina CCL11/análise , Quimiocina CCL24/análise , Quimiocina CCL26/análise , Citocinas/análise , Dermatite/imunologia , Eosinofilia/imunologia , Eosinófilos/imunologia , Epiderme/imunologia , Epiderme/patologia , Humanos , Imuno-Histoquímica , Queratinócitos/imunologia , Queratinócitos/patologia , Estudos Retrospectivos
11.
J Dermatol Sci ; 95(1): 2-7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31272851

RESUMO

The human skin is populated by recirculating T cells and skin-sessile resident memory T cells (TRM). Skin TRM are constructed during immune responses against antigens that the host immune system encounters in the skin. TRM persist in the same sites for a long time and play important protective roles in skin immune responses in collaboration with other skin-composing cells such as dendritic cells and keratinocytes. These TRM with strong effector functions possibly also engender skin inflammatory disorders. Since human skin T cells, especially TRM, are phenotypically distinct from T cells in the blood circulation, T cells residing in the skin should be directly investigated, without presuming from the activities of blood T cells, in order to understand the functional characteristics of skin T cells in skin disorders. This review summarizes the features of human skin TRM and reviews the immunopathological involvement of TRM in human skin disorders such as infectious disease, inflammatory skin disease, and malignant skin tumors.


Assuntos
Dermatite/imunologia , Memória Imunológica , Dermatopatias Infecciosas/imunologia , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Dermatite/sangue , Dermatite/patologia , Humanos , Pele/imunologia , Pele/patologia , Dermatopatias Infecciosas/sangue , Dermatopatias Infecciosas/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Linfócitos T/metabolismo
12.
Acta Derm Venereol ; 99(11): 953-959, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31321443

RESUMO

Wolf's isotopic response refers to the occurrence of a new skin disease at the exact site of an unrelated skin disease that had previously healed. Various cutaneous lesions have been described after herpes zoster. This study included 24 patients with Wolf's isotopic response after herpes zoster infection, which presented as manifestations ranging from inflammatory disease to carcinoma. Histopathological examinations in 12 patients and immunohistochemical analyses in 10 patients allowed exploration of secondary microscopic changes in the lesions. CD4+/CD8+ T-cell ratios were normal and infiltrating cells included mast cells, eosinophils, and tumour cells. Our study has described additional patients with confirmed Wolf's isotopic response following herpes zoster infection; moreover, it has extended the spectrum of Wolf's isotopic response to include impetigo. We suggest Wolf's isotopic response classification categories for herpes zoster-associated Wolf's isotopic response. Additionally, clinicians should consider the possibilities of different diseases in Wolf's isotopic response, especially malignancies.


Assuntos
Herpes Zoster/virologia , Herpesvirus Humano 3/patogenicidade , Dermatopatias/imunologia , Pele/imunologia , Adulto , Idoso , Dermatite/imunologia , Dermatite/patologia , Feminino , Herpes Zoster/imunologia , Herpes Zoster/patologia , Humanos , Impetigo/imunologia , Impetigo/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pele/patologia , Pele/virologia , Dermatopatias/patologia , Dermatopatias/cirurgia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Adulto Jovem
13.
J Dermatol Sci ; 95(1): 13-20, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213388

RESUMO

BACKGROUND: Dietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne. OBJECTIVE: To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis. METHODS: C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling. RESULTS: Mice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines. CONCLUSION: In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.


Assuntos
Ácidos e Sais Biliares/metabolismo , Dermatite/imunologia , Dieta Ocidental/efeitos adversos , Células Th17/imunologia , Células Th2/imunologia , Animais , Proliferação de Células , Resina de Colestiramina/administração & dosagem , Dermatite/tratamento farmacológico , Dermatite/patologia , Derme/imunologia , Derme/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Receptores Acoplados a Proteínas-G/metabolismo , Fatores Sexuais , Transdução de Sinais/imunologia , Organismos Livres de Patógenos Específicos , Receptores de Esfingosina-1-Fosfato/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo
14.
Daru ; 27(1): 283-293, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31129807

RESUMO

BACKGROUND: Atopic dermatitis is a multifactorial immune-mediated skin disorder characterized by an alteration of epidermal barrier function and onset of skin lesions, which range from mild erythema to severe lichenification. Treatment consists in hydration with possible use of topical or immunomodulatory corticosteroids, which, however sometimes showed side effects. Recently, the interest in natural compounds has grown significantly and among these, hydroxytyrosol (HT) plays a pivotal role due to its strong and well-known anti-inflammatory activity. OBJECTIVES: The aim of this study was to investigate the safety and efficacy of Fenolia® Eudermal Cream 15 (HT-based formulation) on epidermal barrier impaired as consequence of skin injury. METHODS: Whit this purpose, morphologic and structural as well as anti-inflammatory evaluations, after treatment with pro-inflammatory mediators (PBS 1 X and LPS) and HT-based formulation on reconstructed human epidermis (RHE) were carried out by qualitative (hematoxylin/eosin- and immunostaining) and quantitative (MTT assay, IL-1α and IL-8 release by ELISA) techniques. Furthermore, HT absorption through the epidermal barrier was evaluated by RP-LC-DAD analysis. RESULTS: A rise in the thickness of the epidermis as well as an appropriate maturation and protein expression (Loricrin, Fillagrin, E-Cadherin and Cytokeratins 5&6) were detected in treated RHE samples. In particular, the HT-based formulation was found to stimulate cell proliferation, as evidenced by the significant increase in Ki67 expression, which suggests the involvement of repair mechanisms, increasing epithelial regeneration and differentiation and improving the epidermal barrier effect. Furthermore, HT-based formulation showed a statistically significant anti-inflammatory activity by reducing both IL-1α and IL-8 release by RHE tissues, greater than the reference drug dexamethasone. Finally, excellent transcutaneous absorption values were found for HT, demonstrating how this new formulation increases the availability of the bioactive compound. CONCLUSIONS: In light of these results, Fenolia® Eudermal Cream 15 could be an effective agent to counteract atopic dermatitis. Graphical abstract Safety and efficacy of hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model.


Assuntos
Dermatite/prevenção & controle , Epiderme/imunologia , Lipopolissacarídeos/efeitos adversos , Álcool Feniletílico/análogos & derivados , Administração Tópica , Sobrevivência Celular/efeitos dos fármacos , Dermatite/imunologia , Composição de Medicamentos , Epiderme/efeitos dos fármacos , Humanos , Modelos Biológicos , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Absorção Cutânea , Creme para a Pele
15.
Eur J Dermatol ; 29(S1): 19-24, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973332

RESUMO

Over the last years, several immune pathways in the skin have been identified. These discoveries have been translated into targeted therapies for inflammatory skin diseases, which have revolutionized our clinical practice. The perturbed molecular network in the skin may serve as a biomarker for disease prediction and as a source of targets for early therapeutic intervention or prevention. With rising costs, this disease-focused healthcare model will become unsustainable, therefore next-generation healthcare must not focus solely on treatment personalisation (the right treatment for the right patient), but also needs to shift its focus towards disease prevention and early therapeutic intervention prior to disease manifestation.


Assuntos
Imunidade Adaptativa/imunologia , Dermatite/imunologia , Dermatite/terapia , Imunidade Inata/imunologia , Pele/imunologia , Humanos , Medicina de Precisão , Fatores de Risco
16.
J Dermatol Sci ; 93(3): 168-175, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30904352

RESUMO

BACKGROUND: Malassezia is one of the commensal microorganisms colonized on human skin and has been shown to be related to several inflammatory cutaneous disorders. Previous studies indicated that Malassezia. sympodialis (M. sympodialis) can produce extracellular vesicles, however, the immunoregulatory function of Malassezia extracellular vesicles on keratinocytes has not been studied. OBJECTIVE: To investigate the extracellular vesicular production capability of Malassezia. furfur (M. furfur) and examine their immunoregulatory effects both in vitro and in vivo. METHODS: Extracellular vesicles derived from M. furfur were isolated by sequential ultracentrifugation procedure. Their structure and diameter were determined by negative stain TEM and NTA, respectively. Confocal microscopy was used to visualize the internalization of these nanoparticles into HaCaT cells and mice epidermal keratinocytes. The expressions of inflammatory cytokines were screened using PCR Array assay and validated in vitro by qPCR and ELISA assays. In vivo cytokine production was measured by the IHC method. The role of NF-κB in such process was evaluated in HaCaT cells by western blot assay. RESULTS: Our results showed that M. furfur produced ovoid-shaped nanoparticles, which could be then internalized into HaCaT cells, as well as mice epidermal keratinocytes. IL-6 expression was significantly enhanced in response to extracellular vesicular stimulation both in vitro and in vivo, in which process the activation of NF-κB was involved. CONCLUSION: M. furfur has the ability to release extracellular vesicles, which can be internalized into keratinocytes and promote the production of IL-6 with the involvement of NF-κB dependent pathway. Such findings reveal some important new insights into Malassezia pathogenesis and therapy.


Assuntos
Dermatite/imunologia , Vesículas Extracelulares/imunologia , Interleucina-6/metabolismo , Queratinócitos/imunologia , Malassezia/imunologia , Animais , Linhagem Celular , Dermatite/microbiologia , Dermatite/patologia , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-6/imunologia , Queratinócitos/metabolismo , Malassezia/citologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , NF-kappa B/metabolismo , Pele/citologia , Pele/imunologia , Pele/microbiologia , Simbiose
19.
J Invest Dermatol ; 139(5): 991-994, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30684557

RESUMO

From June 28-30, 2018, a course entitled "Skin Inflammation in Human Health and Disease: 2018 International Conference" was held in Boston, Massachusetts. In attendance were 107 physicians and scientists from 12 countries. This course was organized by Drs. Rachael Clark, John O'Malley, and Hans Widlund of the Brigham and Women's Hospital, Human Skin Disease Resource Center, Harvard Medical School (Boston, MA). The key findings reported at the meeting are summarized here.


Assuntos
Congressos como Assunto , Dermatite/epidemiologia , Dermatologistas/estatística & dados numéricos , Nível de Saúde , Boston , Dermatite/imunologia , Dermatite/fisiopatologia , Feminino , Humanos , Imunidade Inata , Internacionalidade , Masculino , Dermatopatias/diagnóstico , Dermatopatias/epidemiologia , Dermatopatias/terapia
20.
J Dermatol ; 46(3): 263-266, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628111

RESUMO

Many women experience some skin reaction or trouble in their monthly menstrual cycle, including the exacerbation of pre-existing diseases and skin eruptions directly associated with sex hormones. We herein report a Japanese woman who experienced repeated systemic urticaria in her premenstrual period, and was diagnosed as having estrogen dermatitis based on a positive result of intradermal estrogen skin test. Of note, the expression of estrogen receptor-ß was increased in small dermal vessels of this case as well as in those of patients with other inflammatory skin diseases. These results suggest that inflammation may induce estrogen receptor-ß expression in small dermal vessels, which potentially modifies the pathological skin inflammation during the menstrual period, leading to the development of estrogen dermatitis.


Assuntos
Dermatite/imunologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/imunologia , Ciclo Menstrual/imunologia , Urticária/imunologia , Dermatite/diagnóstico , Dermatite/patologia , Receptor beta de Estrogênio/análise , Estrogênios/metabolismo , Feminino , Humanos , Testes Intradérmicos/métodos , Pessoa de Meia-Idade , Pele/patologia , Urticária/diagnóstico , Urticária/patologia
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