Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs
| Autor: | Yifei Wang, Melanie J. Scott, Haiyan Xu, Robert J. Binder, Sudesh Pawaria, Abigail L. Sedlacek |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes Immunology Interleukin-1beta Antigen-Presenting Cells Endogeny chemical and pharmacologic phenomena Apoptosis 03 medical and health sciences Mice 0302 clinical medicine Immune system In vivo Heat shock protein NLR Family Pyrin Domain-Containing 3 Protein medicine Immunology and Allergy Animals Cells Cultured Inflammation Mice Knockout Membrane Glycoproteins Chemistry Caspase 1 Intracellular Signaling Peptides and Proteins Inflammasome Dendritic Cells Phosphate-Binding Proteins Cell biology Mice Inbred C57BL 030104 developmental biology Potassium Cutting Edge Efflux Signal transduction Apoptosis Regulatory Proteins 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 201(8) |
| ISSN: | 1550-6606 |
| Popis: | Several heat shock proteins (HSPs) prime immune responses, which are, in part, a result of activation of APCs. APCs respond to these immunogenic HSPs by upregulating costimulatory molecules and secreting cytokines, including IL-1β. These HSP-mediated responses are central mediators in pathological conditions ranging from cancer, sterile inflammation associated with trauma, and rheumatoid arthritis. We tested in this study the requirement of inflammasomes in the release of IL-1β by one immunogenic HSP, gp96. Our results show that murine APCs activate NLRP3 inflammasomes in response to gp96 by K+ efflux. This is shown to initiate inflammatory conditions in vivo in the absence of additional known inflammasome activators or infection. These results document a novel mechanism by which proteins of endogenous origin, the HSPs, can modulate an inflammatory response following their release from aberrant cells. |
| Databáze: | OpenAIRE |
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