RESUMO
Interferons are a family of pleiotropic cytokines, their name was assigned because of their anti-replicative viral activity. IFNgamma or immune type II interferon does not share receptors with the type I interferon, its structure is different and its gene is located in different chromosome, although its biologic effects are similar. Along of several years of research, it has been found that IFNgamma enhances the transcription of genes involved in immunomodulation, antiviral responses and antitumoral activities. Regarding to the immune system, IFNgamma increases the cytotoxic and phagocytic activity of macrophages and upregulates the expression of major histocompatibility complex (MHC) class I and class II molecules in dendritics cells and other antigen presenting cells. IFNgamma also promotes the development and differentiation of naive CD4+ T lymphocytes to Th1 helper subset. Indeed, this cytokine has a key role in the control of bacterial, micotic, viral and parasitic infections. Depending of the micro-environment, IFNgamma has a dual role as pro or anti inflammatory cytokine. Novel therapeutic strategies are currently being developed with the aim to enhance the immune response or replace IFNgamma gene abnormal expression with beneficial results in humans, being recombinant IFNgamma safe and well tolerated.
Assuntos
Interferon gama/fisiologia , Animais , Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/terapia , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica , Doença Granulomatosa Crônica/terapia , Humanos , Fatores Imunológicos/uso terapêutico , Infecções/fisiopatologia , Infecções/terapia , Inflamação/fisiopatologia , Inflamação/terapia , Interferon gama/antagonistas & inibidores , Interferon gama/química , Interferon gama/genética , Interferon gama/uso terapêutico , Janus Quinases/fisiologia , Camundongos , Camundongos Knockout , Neoplasias/fisiopatologia , Neoplasias/terapia , Conformação Proteica , Ratos , Receptores de Interferon/química , Receptores de Interferon/fisiologia , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais/fisiologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Receptor de Interferon gamaRESUMO
We describe a universal ligand-binding receptor for human interferons alpha and interferon beta (type I IFNs). A soluble 40 kDa IFN-alpha/beta receptor (p40) that blocks the activity of type I IFNs was purified from urine and sequenced. Antibodies raised against p40 completely block the activity of several type I IFNs and immuno-precipitate both a cellular 102 kDa IFN-alpha/beta receptor and its cross-linked complexes with IFN-alpha 2. The receptor is a disulfide-linked dimer, consisting of 51 kDa subunits. We isolated and expressed a 1.5 kb cDNA, coding for the IFN-alpha/beta receptor. Its 331 amino acid sequence includes a leader and a transmembrane region, while its ectodomain corresponds to p40. IFN-alpha/beta receptor is physically associated with the cytoplasmic Tyr kinase JAK1, hence, in addition to ligand binding, it is directly involved in signal transduction.