Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes. | Bryan et al. Journal of Inflammation 2010 7 23 http content 7 1 23 JOURNAL OF INFLAMMATION RESEARCH Open Access Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain ASC regulates inflammasomes Nicole B Bryan21 2 Andrea Dorfleutner21 Sara J Kramer 1 Chawon Yun1 Yon Rojanasakul3 and Christian Stehlik 1 Abstract Background The apoptotic speck-like protein containing a caspase recruitment domain ASC is the essential adaptor protein for caspase 1 mediated interleukin IL -1P and IL-18 processing in inflammasomes. It bridges activated Nod like receptors NLRs which are a family of cytosolic pattern recognition receptors of the innate immune system with caspase 1 resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1p. Furthermore we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response which triggers IL-1P processing and secretion. However the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor. Methods To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors IL-1P processing and secretion was investigated by ELISA in inflammasome reconstitution assays stable expression in THP-1 and J774A1 cells and by restoring the lack of endogenous ASC in mouse macrophages. In addition the localization of ASC and ASC isoforms was determined by immunofluorescence staining. Results The three novel ASC isoforms ASC-b ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor with one of the
