Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments

The protein NLRP3 has emerged as a central regulator in the inflammatory process, being implicated directly in hereditary cryopyrinopathies, and indirectly in diseases such as gout, Type 2 diabetes and atherosclerosis. NLRP3 is an important regulator of caspase-1, the enzyme that processes the immature form of IL-1β into the active protein. The control of NLRP3 has therefore become a focus of research with evidence for redox regulation, ubiquitination and regulation by miRNA-223, kinases and calcium all emerging as controllers of NLRP3. As our knowledge expands the prospect for precise pharmacological targeting of NLRP3 will improve and could lead to substantial clinical utility.

► Overview of the control of NLRP3 activity by the cellular redox environment.
► miRNA-223 and viral factors can inhibit NLRP3.
► Kinase and calcium signalling are emerging as regulators of NLRP3 activation.
► Outline of recent findings on ubiquitination and the mechanism of NLRP3 priming.
► Discussion of pharmacological manipulation of NLRP3 inflammasome activity.