Silica Crystals and Aluminum Salts Regulate the Production of Prostaglandin in Macrophages via NALP3 Inflammasome-Independent Mechanisms

Abstract

Particulates such as silica crystal (silica) and aluminum salts (alum) activate the inflammasome and induce the secretion of proinflammatory cytokines in macrophages. These particulates also induce the production of immunoglobulin E via a T helper 2 (Th2) cell-associated mechanism. However, the mechanism involved in the induction of type 2 immunity has not been elucidated. Here, we showed that silica and alum induced lipopolysaccharide-primed macrophages to produce the lipid mediator prostaglandin E₂ (PGE₂) and interleukin-1β (IL-1β). Macrophages deficient in the inflammasome components caspase 1, NALP3, and ASC revealed that PGE₂ production was independent of the NALP3 inflammasome. PGE₂ expression was markedly reduced in PGE synthase-deficient (Ptges⁻/⁻) macrophages, and Ptges⁻/⁻ mice displayed reduced antigen-specific serum IgE concentrations after immunization with alum or silica. Our results indicate that silica and alum regulate the production of PGE₂ and that the induction of PGE₂ by particulates controls the immune response in vivo.

Monosodium urate crystals trigger Nrf2- and heme oxygenase-1-dependent inflammation in THP-1 cells

“…Either NADPH oxidase or cyclooxygenase-2 (COX-2) is believed to contribute to ROS production in response to NLRP3-mediated inflammation. 15,16 The expression levels of p47phox, a subunit of NADPH oxidase and of COX-2 were analyzed by western blotting techniques. The levels of cytosolic p47phox and COX-2 proteins were increased in response to MSU in a dosedependent manner (Supplementary Figure 1).…”

NLRP3 inflammasome–mediated neutrophil recruitment and hypernociception depend on leukotriene B4 in a murine model of gout

“…However, it is important to mention that other mediators and cell types not analyzed in the present study could contribute to MSU crystal-induced hypernociception. For example, a recent study demonstrated that particulate materials, including silica crystals and aluminum salt, are able to induce prostaglandin E 2 production independent of the NLRP3 inflammasome (40).…”

Chlorophyll Concentration and Morphological Diversity in Corn Lines at Different Vegetative Stages

“…Potassium deficiency in plants usually induces brown scorching and curling of leaf tips as well as chlorosis (yellowing) between leaf veins, which accelerate leaf senescence. Leaf photosynthesis consists of the several physiological processes, including light harvesting, photosystem II (PSII) photochemistry and CO2 assimilation [7]. Chlorophyll fluorescence measurements have increasingly been used as a non-invasive tool in leaf ecophysiological studies.…”