6 research outputs found

    Studies of specific gene induction during apoptosis of cell lines conditionally immortalized by SV40

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    International audienceInactivation of SV40 large T antigen, in cells immortalized with conditional mutants, leads to activation of p53 and apoptosis. We have analyzed during this process the expression of genes induced by p53 or differentially expressed during apoptosis in other systems. We find an early induction of Waf1/Cip1. We also observed clusterin is induced late during the process and displays a high level of expression in non-apoptotic cells suggesting a protective role for clusterin. Other genes identified during thymocyte and lymphocyte apoptosis are not induced, showing that the pattern of gene induction is specific to the system studied

    Lessons on SpA pathogenesis from animal models

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    International audienceUnderstanding the complex mechanisms underlying a disorder such as spondyloarthritis (SpA) may benefit from studying animal models. Several suitable models have been developed, in particular to investigate the role of genetic factors predisposing to SpA, including HLA-B27, ERAP1, and genes related to the interleukin (IL)-23/IL-17 axis. One of the best examples of such research is the HLA-B27 transgenic rat model that fostered the emergence of original theories regarding HLA-B27 pathogenicity, including dysregulation of innate immunity, contribution of the adaptive immune system to chronic inflammation, and influence of the microbiota on disease development. Very recently, a new model of HLA-B27 transgenic Drosophila helped to expand further some of those theories in an unexpected direction involving the TGFβ/BMP family of mediators. On the other hand, several spontaneous, inducible, and/or genetically modified mouse models-including SKG mouse, TNFΔARE mouse and IL-23-inducible mouse model of SpA-have highlighted the importance of TNFα and IL-23/IL-17 axis in the development of SpA manifestations. Altogether, those animal models afford not only to study disease mechanism but also to investigate putative therapeutic targets
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