RESUMO
Psoriasis is a T cell-dependent autoimmune disease of the skin and joints. Disease manifestation is orchestrated by proinflammatory CD4-positive T helper cells producing either interferon-gamma (Th1) or interleukin (IL)-17 (Th17). These Th1 and Th17 cells interact with dermal dendritic cells, macrophages, mast cells, and neutrophils. Together, they cause an inflammation that mainly involves interferon-gamma, tumor necrosis factor, IL-8, IL-12, IL-17, IL-19, and IL-23. New therapeutics either are directed against T cells, tumor necrosis factor, and IL-12/IL-23 or deviate immune responses into a protective IL-4-dominated Th2 phenotype.
Assuntos
Citocinas/imunologia , Ativação Linfocitária , Psoríase/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Citocinas/metabolismo , Humanos , Macrófagos/imunologia , Mastócitos/imunologia , Psoríase/metabolismo , Psoríase/fisiopatologia , Psoríase/terapia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
The definition of an optimal siRNA results from the in vitro testing of several siRNA designed to specifically target a gene. Usually, such in vitro tests consist in the transfection of the several siRNA duplexes in a cell expressing stably the gene of interest. When a siRNA specific for a mRNA coding toxic proteins (certain transcription factors, transporters, toxins, cell cycle controlling proteins, etc.) must be tested, the generation of a target cell is difficult. Here we report a quick method to test the efficiency of a siRNA through its co-transfection with the targeted mRNA. This technique can be used as a fast method to test siRNA even when they target genes that cannot be stably expressed in the cells of interest.
Assuntos
Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Animais , Células Cultivadas , Células Dendríticas , Eletroporação , Expressão Gênica , Camundongos , TransfecçãoRESUMO
BACKGROUND: Interleukin 4 (IL-4) is the central cytokine driving the differentiation of naive CD4(+) T helper (TH) cells into anti-inflammatory IL-4-producing TH2 cells. In contrast, IL-12/IL-23 promotes the development of TH1/TH17 immune responses that induce organ-specific autoimmune diseases such as psoriasis or multiple sclerosis. OBJECTIVE: We focus on the potential of IL-4 and TH2 induction to treat inflammatory autoimmune diseases. METHODS: Here, we summarize the basics for the establishment of the in vitro and in vivo conditions for the generation of TH2 immune responses, followed by various experimental data showing the therapeutic use of IL-4 for the therapy of autoimmune diseases. This data and early experiences with recombinant human IL-4 (rhIL-4) in the therapy of patients with cancer set the basis for the clinical introduction of rhIL-4 in the treatment of patients with psoriasis in a Phase I/II trial. CONCLUSION: IL-4 seems to act by inducing an anti-inflammatory phenotype and further clinical trials will explore the promising therapeutic potency of IL-4 in psoriasis during the upcoming era of biologics.