RESUMO
Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD.
Assuntos
Catecóis/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Diarileptanoides/uso terapêutico , Pele/patologia , Administração Cutânea , Animais , Catecóis/administração & dosagem , Catecóis/síntese química , Ciclo-Oxigenase 2/sangue , Diarileptanoides/administração & dosagem , Diarileptanoides/síntese química , Diarileptanoides/isolamento & purificação , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Feminino , Imunoglobulina E/sangue , Injeções Intraperitoneais , Interleucinas/sangue , Camundongos , Camundongos Endogâmicos , Óxido Nítrico Sintase Tipo II/sangueRESUMO
BACKGROUND: There is growing evidence of a role of the immune system in the pathophysiology of ischemia-reperfusion (I/R) injury, but the influence of I/R injury on innate immunity is still undetermined. METHODS: Sprague-Dawley rats were used. I/R injury was induced by clamping both renal arteries for 45 min, and the rats were killed 1, 3, 5, and 7 days later. Activation of innate immunity was evaluated in terms of the expression of toll-like receptor (TLR) 2 or TLR4 mRNAs and protein, by the level of the TLR ligand (heat shock protein [HSP] 70), and maturation of dendritic cells by double-label immunohistochemistry of dendritic cells for major histocompatibility complex (MHC) class II antigen. RESULTS: I/R injury increased TLR2 and TLR4 mRNA and protein expression, and they were mainly observed on renal tubular cells. I/R injury also produced endogenous TLR ligand (HSP70) on renal tubular cells. I/R injury increased not only the numbers of dendritic cells but also the production of MHC class II antigen in dendritic cells, suggesting maturation of these cells. Activation of innate immunity was observed at day 1, peaked at days 3 to 5 after I/R injury, and thereafter gradually decreased. CONCLUSIONS: I/R injury rapidly activates the innate immune response.
Assuntos
Imunidade Inata , Rim/imunologia , Traumatismo por Reperfusão/imunologia , Animais , Formação de Anticorpos , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Proteínas de Choque Térmico HSP70/metabolismo , Antígenos de Histocompatibilidade Classe II/biossíntese , Antígenos de Histocompatibilidade Classe II/metabolismo , Rim/patologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Receptores Toll-LikeRESUMO
BACKGROUND: Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy. METHODS: Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II). RESULTS: FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment. CONCLUSIONS: FTY720 treatment prevents CsA-induced renal injury.