title: 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.
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka 807-8555, Japan. kuroetu@med.uoeh-u.ac.jp
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohata
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003460:Crystallization; D058847:Inflammasomes / Q000276:immunology*; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010588:Phagosomes / Q000276:immunology; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000096:biosynthesis* / Q000276:immunology; D012822:Silicon Dioxide / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011453:Prostaglandins; D012822:Silicon Dioxide; D000535:Aluminum; D020170:Caspase 1; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse