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Immunity. 2011 Apr 22;34(4):514-26. doi: 10.1016/j.immuni.2011.03.019. Epub 2011 Apr 14.

Silica crystals and aluminum salts regulate the production of prostaglandin in macrophages via NALP3 inflammasome-independent mechanisms.

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  • 1Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka 807-8555, Japan.


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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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