NLRP3 inflammasome-mediated toxicity of fibrous particles

Abstract

Long airborne fibers such as asbestos and carbon nanotubes (CNTs) are more potent activators of carcinogenesis, inflammation, and genotoxicity than short or tangled fibers. It has recently been reported that fibrous particles trigger the secretion of proinflammatory cytokines such as interleukin (IL)-1β and IL-18 and cause inflammatory diseases through the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. The NLRP3 inflammasome is a major component of the innate immune system in responses to infection and tissue injury in phagocytotic cells. The shape, size, charge, and biopersistence of particulate substances are the most important factors affecting their ability to cause NLRP3 inflammasome-mediated proinflammatory responses. In this review, the current understandings are summarized and discussed regarding the mechanisms of NLRP3 inflammasome induction by various fibrous particles. In addition, the review demonstrates the potential mechanism of IL-1β secretion through the NLRP3 inflammasome, with a focus on the role of the GTPase effector Rho kinases (ROCK1 and 2), which are known to be involved in a wide range of cellular functions including adhesion, regulation of the cytoskeleton, and phagocytosis.