RESUMO
Psoriasis and atopic dermatitis are inflammatory skin diseases, and these patients have an increased risk of cardiovascular events and other medical complications. It has been clarified that skin inflammation affects internal organs. Additionally, dental caries tends to occur more frequently in patients with psoriasis and atopic dermatitis. In this study, we aim to investigate the effects of dermatitis on the salivary glands using an inflammation model mouse. Salivary secretion stimulated with pilocarpine was reduced in dermatitis mice. Histologically, dermatitis mice showed amyloid deposition, glandular atrophy, and fibrosis in the salivary glands. Expression of inflammatory cytokines in the salivary glands was higher in dermatitis mice; however, secretion of cytokines in saliva was not significantly different. Dermatitis mice showed decreased salivary secretion and histological changes, which may cause periodontal disease. Therefore, appropriate control of skin inflammation is essential.
Assuntos
Cárie Dentária , Dermatite Atópica , Psoríase , Animais , Atrofia/patologia , Citocinas/metabolismo , Cárie Dentária/patologia , Dermatite Atópica/patologia , Humanos , Inflamação/patologia , Camundongos , Psoríase/patologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologiaRESUMO
Secondary osteoporosis can also be caused by chronic inflammatory skin disease as well as rheumatoid arthritis or inflammatory bowel disease. However, the exact role of osteoporosis in inflammatory skin conditions has not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of osteoporosis in inflammatory skin conditions and the therapeutic impact of osteoporosis medication on inflammatory skin disease. We employed model mice of spontaneous skin inflammation, specifically overexpressing human caspase-1 in the epidermis. Bone density and the expression of various mRNAs in the femur were examined by micro CT and RT-PCR. The effects of minodronate and anti-RANKL antibody on bone structure, histology, and femur blood flow were studied. The mouse model of skin inflammation showed a marked decrease in bone density compared to wild-type littermates with abnormalities in both bone resorption and formation. Minodronate improved bone density by decreasing osteoclasts, but anti-RANKL antibody did not improve. In the dermatitis model, the blood flow in the bone marrow was decreased, and minodronate restored this parameter. A model of persistent dermatitis exhibited marked osteoporosis, but the impact of chronic dermatitis on osteoporosis has not been thoroughly investigated. We should explore the pathogenesis of osteoporosis in skin inflammatory diseases.
Assuntos
Citocinas/metabolismo , Osteoporose/metabolismo , Psoríase/metabolismo , Animais , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Caspase 1/metabolismo , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Feminino , Fêmur/irrigação sanguínea , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Psoríase/complicações , Fluxo Sanguíneo RegionalRESUMO
Psoriasis is one of the common chronic inflammatory skin diseases in which inflammatory cytokines such as IL-17 and TNF-α play critical roles. Skin microbiome of psoriasis patients is reported to have elevated Staphylococcus and Streptococcus genus. There are controversial reports about gut microbiome of psoriasis patients, and whether the diversity of bacteria in genus level is decreased or not is still unclear. Moreover, it is not yet known if these gut bacteria would be the cause of the inflammation or the result of the inflammation. We analyzed the gut microbiome of the inflammatory skin model mouse (keratinocyte-specific caspase-1 transgenic (Kcasp1Tg) mouse), by analyzing the 16S rRNA gene. Staphylocuccus aureus and Streptococcus danieliae were abundant in Kcasp1Tg mouse fecal microbiome. These dominant bacteria as well as recessive control bacteria were orally administrated to antibiotic-treated wild type mice, and set up imiquimod-induced psoriasis-like skin inflammation model. The skin inflammation including ear thickness and histopathological findings was analyzed. The exacerbated skin lesions with the elevated levels of TNF-α, IL-17A, IL-17F, and IL-22 were observed in Staphylocuccus aureus and Streptococcus danieliae administrated groups. Our finding suggests that there is affinity between skin inflammation severity and certain gut bacteria leading to a vicious cycle: skin inflammation populates certain gut bacteria which itself worsens the skin inflammation. This is the first report on Staphylocuccus aureus and Streptococcuus danieliae effects in vivo. Not only treating the skin lesion but also treating the gut microbiome could be the future key treatment for inflammatory skin disease such as psoriasis.
Assuntos
Citocinas/genética , Imiquimode/efeitos adversos , Psoríase/microbiologia , Staphylococcus aureus/isolamento & purificação , Streptococcus/isolamento & purificação , Administração Oral , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Fezes/citologia , Feminino , Microbioma Gastrointestinal , Humanos , Interleucina-17/genética , Interleucinas/genética , Camundongos , Psoríase/induzido quimicamente , Psoríase/genética , Psoríase/imunologia , RNA Ribossômico 16S/genética , Staphylococcus aureus/genética , Staphylococcus aureus/imunologia , Streptococcus/genética , Streptococcus/imunologia , Fator de Necrose Tumoral alfa/genética , Regulação para Cima , Interleucina 22RESUMO
: Adipose tissue (AT) is the largest endocrine organ, producing bioactive products called adipocytokines, which regulate several metabolic pathways, especially in inflammatory conditions. On the other hand, there is evidence that chronic inflammatory skin disease is closely associated with vascular sclerotic changes, cardiomegaly, and severe systemic amyloidosis in multiple organs. In psoriasis, a common chronic intractable inflammatory skin disease, several studies have shown that adipokine levels are associated with disease severity. Chronic skin disease is also associated with metabolic syndrome, including abnormal tissue remodeling; however, the mechanism is still unclear. We addressed this problem using keratin 14-specific caspase-1 overexpressing transgenic (KCASP1Tg) mice with severe erosive dermatitis from 8 weeks of age, followed by re-epithelization. The whole body and gonadal white AT (GWAT) weights were decreased. Each adipocyte was large in number, small in size and irregularly shaped; abundant inflammatory cells, including activated CD4+ or CD8+ T cells and toll-like receptor 4/CD11b-positive activated monocytes, infiltrated into the GWAT. We assumed that inflammatory cytokine production in skin lesions was the key factor for this lymphocyte/monocyte activation and AT dysregulation. We tested our hypothesis that the AT in a mouse dermatitis model shows an impaired thermogenesis ability due to systemic inflammation. After exposure to 4 °C, the mRNA expression of the thermogenic gene uncoupling protein 1 in adipocytes was elevated; however, the body temperature of the KCASP1Tg mice decreased rapidly, revealing an impaired thermogenesis ability of the AT due to atrophy. Tumor necrosis factor (TNF)-α, IL-1ß and interferon (INF)-γ levels were significantly increased in KCASP1Tg mouse ear skin lesions. To investigate the direct effects of these cytokines, BL/6 wild mice were administered intraperitoneal TNF-α, IL-1ß and INF-γ injections, which resulted in small adipocytes with abundant stromal cell infiltration, suggesting those cytokines have a synergistic effect on adipocytes. The systemic dermatitis model mice showed atrophy of AT and increased stromal cells. These findings were reproducible by the intraperitoneal administration of inflammatory cytokines whose production was increased in inflamed skin lesions.
Assuntos
Citocinas/fisiologia , Dermatite/patologia , Gordura Intra-Abdominal/patologia , Células Estromais/efeitos dos fármacos , Adipócitos/patologia , Adipocinas/biossíntese , Adipocinas/genética , Tecido Adiposo Branco/patologia , Animais , Atrofia , Caspase 1/fisiologia , Tamanho Celular , Temperatura Baixa , Citocinas/biossíntese , Citocinas/toxicidade , Dermatite/imunologia , Dermatite/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação , Gordura Intra-Abdominal/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Monócitos/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Recombinantes/toxicidade , Células Estromais/metabolismo , Subpopulações de Linfócitos T/imunologia , Proteína Desacopladora 1/biossíntese , Proteína Desacopladora 1/genéticaAssuntos
Ciclosporina/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Penfigoide Bolhoso/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Lactente , Masculino , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/patologia , Pele/patologia , Resultado do TratamentoAssuntos
Arteriopatias Oclusivas/etiologia , Fatores Biológicos/uso terapêutico , Encéfalo/metabolismo , Artérias Cerebrais , Dermatite/complicações , Glucose/metabolismo , Animais , Arteriopatias Oclusivas/imunologia , Arteriopatias Oclusivas/metabolismo , Citocinas/metabolismo , Dermatite/tratamento farmacológico , Dermatite/metabolismo , Humanos , Interleucina-1/antagonistas & inibidores , CamundongosRESUMO
A 39-year-old woman presented with prominent and painful livedo reticularis lesions spreading on her upper and lower extremities. Histopathologically, the small-to medium-sized arteries in the deep dermis and subcutis showed necrotizing vasculitis with cellular infiltration, suggesting cutaneous polyarteritis nodosa. The serum levels of inflammatory markers normalized with aspirin 100mg/day and prednisolone 10mg/day within 2 months, and there was no other skin or organ involvement over 18 months of follow up. However, serious refractory skin depressions and pigmentation remained after two years of treatment. This suggests the importance of early and aggressive therapy for cutaneous polyarteritis nodosa to prevent unsightly skin sequel, as well as control of disease activity.
Assuntos
Livedo Reticular/complicações , Transtornos da Pigmentação/etiologia , Poliarterite Nodosa/complicações , Adulto , Biópsia , Feminino , Humanos , Livedo Reticular/tratamento farmacológico , Livedo Reticular/patologia , Transtornos da Pigmentação/patologia , Poliarterite Nodosa/tratamento farmacológico , Poliarterite Nodosa/patologia , Pele/patologia , Resultado do TratamentoAssuntos
Dermatite/imunologia , Hipergamaglobulinemia/imunologia , Imunoglobulina G/metabolismo , Agregação Patológica de Proteínas/imunologia , Animais , Caspase 1/genética , Dermatite/sangue , Dermatite/patologia , Modelos Animais de Doenças , Feminino , Humanos , Hipergamaglobulinemia/sangue , Hipergamaglobulinemia/patologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Agregação Patológica de Proteínas/sangue , Agregação Patológica de Proteínas/patologiaAssuntos
Dessensibilização Imunológica , Vetores Genéticos/imunologia , Interleucina-10/imunologia , Mucosa Nasal/imunologia , Paramyxoviridae/imunologia , Rinite Alérgica Sazonal/imunologia , Animais , Modelos Animais de Doenças , Vetores Genéticos/genética , Humanos , Interleucina-10/genética , Leucócitos/imunologia , Leucócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Mucosa Nasal/patologia , Paramyxoviridae/genética , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/patologia , Rinite Alérgica Sazonal/terapiaRESUMO
Abstract: A 39-year-old woman presented with prominent and painful livedo reticularis lesions spreading on her upper and lower extremities. Histopathologically, the small-to medium-sized arteries in the deep dermis and subcutis showed necrotizing vasculitis with cellular infiltration, suggesting cutaneous polyarteritis nodosa. The serum levels of inflammatory markers normalized with aspirin 100mg/day and prednisolone 10mg/day within 2 months, and there was no other skin or organ involvement over 18 months of follow up. However, serious refractory skin depressions and pigmentation remained after two years of treatment. This suggests the importance of early and aggressive therapy for cutaneous polyarteritis nodosa to prevent unsightly skin sequel, as well as control of disease activity.