title: A genetically encoded IL-1β bioluminescence resonance energy transfer sensor to monitor inflammasome activity.
abstract: Inflammation is fundamental for protecting the organism against infection and injury. However, a failure to control immune response results in chronic inflammation and several associated disorders such as pain and loss of function. Initiation of inflammation is orchestrated by cytokines, among which IL-1β is particularly important. IL-1β is synthesized as an inactive protein that has to be processed by the inflammasome to generate the mature bioactive form. Conventional techniques cannot monitor IL-1β activation with high spatial and temporal resolution. In this study, we present a ratiometric biosensor that allows monitoring IL-1β processing in real time, with a temporal resolution of seconds and with a single-cell spatial resolution. Using this sensor, to our knowledge, we describe for the first time the kinetic of the inflammasome activity in living macrophages. With this new probe, we also demonstrated that the pro-IL-1β processing occurs all over the cytoplasm.
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. vincent.compan@manchester.ac.uk
authors: Vincent
authors: V
authors: Compan
authors: Alberto
authors: A
authors: Baroja-Mazo
authors: Laricia
authors: L
authors: Bragg
authors: Alexei
authors: A
authors: Verkhratsky
authors: Julie
authors: J
authors: Perroy
authors: Pablo
authors: P
authors: Pelegrin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004735:Energy Transfer / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism*; D049410:Luciferases, Renilla / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008164:Luminescent Proteins; D011498:Protein Precursors; C054562:yellow fluorescent protein, Bacteria; D049410:Luciferases, Renilla