Nes, adhesion molecules, and so on. This functional memory contributes considerably
Nes, adhesion molecules, and so on. This functional memory contributes considerably to the chronicity of inflammation and its eventual refraction to therapy. Here, we describe the global gene expression profiles of in vitro repeatedly reactivated murine Th1 and Th2 cells, and compare them with those of na e and once activated Th1 and Th2 cells, both before and after re-stimulation (Fig. 1). Among differentially expressed genes is a novel transcription factor, which downmodulates NF-B signalling and is exclusively expressed in repeatedly re-activated Th1 cells. High expression of this gene can be detected in Th cells isolated from the site of inflammation of patients suffering from distinct forms of rheumatic diseases or ulcerative colitis, but not in Th cells isolated from healthy tissue or from blood. Expression of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28549975 this gene in Th cells at the site of inflammation highlights the role of chronic T-cell activation in chronic inflammation and may represent an endogenous mechanism to limit inflammation. Apart from its diagnostic value, this molecular pathway also points to a new therapeutic target.P91 Intracellular IL-1 receptor antagonist (icIL-1Ra1) does not antagonize growth inhibitory effects of pre-IL-1 in SaOS-2 cellsG Palmer, S Trolliet, D Talabot-Ayer, F M in, D Magne, C Gabay Division of Rheumatology, University Hospital of Geneva and Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland Arthritis Res Ther 2005, 7(Suppl 1):P91 (DOI 10.1186/ar1612) Background IL-1 is synthesized as a precursor (preIL-1), which is processed into mature IL-1 and a N-terminal propeptide by calpain-like proteases. Besides its classical PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27741243 effects elicited upon IL-1 receptor binding, preIL-1 exerts intracellular functions, including the modulation of cell growth and apoptosis. Nuclear translocation of preIL-1, mediated by the N-terminal propeptide, is required for these effects. IL-1 receptor antagonist (IL-1Ra) inhibits the classical effects of IL-1 by preventing the interaction of IL-1 with its receptor. Four different isoforms of IL-1Ra have been described, of which one is secreted and three others are intracellular (icIL-1Ra1, icIL-1Ra 2, icIL-1Ra 3). Due to their intracellular localization, icIL-1Ras cannot interact with cell Oroxylin A site surface receptors and have been suggested to carry out specific functions inside cells. The description of nuclear functions for preIL-1 suggested that icIL1Ra variants might antagonize intracellular effects of preIL-1. Objective and methods The aim of this study was to investigate effects of preIL1 and icIL-1Ra1 on cell growth using stably transfected SaOS-2 osteosarcoma cells. IL-1 and IL-1Ra expression was quantified by ELISA and their localization was examined by immunofluorescence. Cell counts, lactate dehydrogenase activity and [3H]-thymidine incorporation were used to monitor cell growth. Results IL-1 expression ranged from 5.3 to 9.4 ng/106 cells in culture supernatants and from 39.8 to 87.3 ng/106 cells in lysates of preIL-1 transfected SaOS-2 cells. Immunostaining showed nuclear localization of preIL-1, which was not modified by co-transfection of icIL-1Ra1. Expression levels of IL-1Ra ranged from 53 to 219 ng/106 cells in supernatants and from 1678 to 4414 ng/106 cells in lysates of icIL-1Ra1 transfected cells. IL-1Ra staining was essentially cytoplasmic. Transfection of SaOS-2 cells with preIL-1 significantly decreased cell growth, as indicated by reduced cell counts and.