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Publication : Cell volume regulation modulates NLRP3 inflammasome activation.

First Author  Compan V Year  2012
Journal  Immunity Volume  37
Issue  3 Pages  487-500
PubMed ID  22981536 Mgi Jnum  J:187661
Mgi Id  MGI:5437762 Doi  10.1016/j.immuni.2012.06.013
Citation  Compan V, et al. (2012) Cell Volume Regulation Modulates NLRP3 Inflammasome Activation. Immunity 37(3):487-500
abstractText  Cell volume regulation is a primitive response to alterations in environmental osmolarity. The NLRP3 inflammasome is a multiprotein complex that senses pathogen- and danger-associated signals. Here, we report that, from fish to mammals, the basic mechanisms of cell swelling and regulatory volume decrease (RVD) are sensed via the NLRP3 inflammasome. We found that a decrease in extracellular osmolarity induced a K(+)-dependent conformational change of the preassembled NLRP3-inactive inflammasome during cell swelling, followed by activation of the NLRP3 inflammasome and caspase-1, which was controlled by transient receptor potential channels during RVD. Both mechanisms were necessary for interleukin-1beta processing. Increased extracellular osmolarity prevented caspase-1 activation by different known NLRP3 activators. Collectively, our data identify cell volume regulation as a basic conserved homeostatic mechanism associated with the formation of the NLRP3 inflammasome and reveal a mechanism for NLRP3 inflammasome activation.
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