RESUMEN
The common gamma chain (gammac) is the central signaling unit for a number of cytokine receptors collectively known as the gammac cytokine receptor family. gammac is critical for ligand binding and signaling by gammac cytokines. gammac cytokine signaling had been thought to be mainly regulated by cytokine-specific receptor alpha chain expression levels with little or no effect by gammac surface levels because gammac expression was presumed to remain unchanged during T-cell activation and development. The extent of gammac cytokine responses is thought to be regulated by cytokine specific receptor subunits and not by the gammac receptor. In contrast to this prevailing view, we have recently reported that gammac itself actively regulates gammac cytokine responses. Interestingly, gammac exerted its regulatory effects not only as a conventional membrane receptor protein but also as a secreted protein whose expression was upregulated upon T-cell stimulation. Here we will review how a soluble form of gammac, which is generated by alternative splicing, regulates gammac cytokine signaling and plays a role in controlling immune activation related to autoimmune disease.
Asunto(s)
Humanos , Empalme Alternativo , Enfermedades Autoinmunes , Citocinas , Membranas , Receptores de Citocinas , Linfocitos TRESUMEN
BACKGROUND: The assay of cytokines and their soluble receptors in the synovial fluid of inflammatory arthropathy may be useful in studying pathogenetic and immunoregulatory mechanisms of different arthritis. The aim of this study is to investigate cytokine profiles in rheumatoid arthritis and to find the characteristic pattern of cytokine concentration in rheumatoid arthritis according to the clinical manifestations. METHODS: We measured the concentration of TNF-alpha, IL-1 beta, IL-2, IL-6, IL-8 and IL-10, soluble TNF receptor I, II, IL-1 soluble receptor 2 and IL-6 soluble receptor in synovial fluid from the patients with rheumatoid arthritis using ELISA method. We compared these data with result from osteoarthritis patients. In rheumatoid arthritis, we investigated differences of cytokine profile according to clinical manifestations such as duration of disease, radiographic bone erosions and existence of rheumatoid factor. RESULTS: All of the concentrations of cytokines except IL-2 were significantly elevated in synovial fluid of rheumatoid arthritis than osteoarthritis. When we grouped RA patients according to existence of rheumatoid factor and compared the concentration of cytokines, there were no significant differences between seropositive and seronegative group. We also compared early and late disease, and erosive and non-erosive group but there were no significant differences in cytokine level. CONCLUSION: Our data support the results from other studies that concentration of pro-inflammatory or anti-inflammatory cytokines were elevated in rheumatoid arthritis than osteoarthritis. However, we cannot find the relationship between clinical findings and cytokine profiles in joint fluid.