title: Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages.
abstract: The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases.
authors.affiliation: Laboratory of Virology and Immunology, GIGA-Signal Transduction.
authors.forename: Laurent
authors.initials: L
authors.lastname: L'homme
authors.forename: Nathalie
authors.initials: N
authors.lastname: Esser
authors.forename: Laura
authors.initials: L
authors.lastname: Riva
authors.forename: André
authors.initials: A
authors.lastname: Scheen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Paquot
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Legrand-Poels
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010168:Palmitates / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013228:Stearates / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D010168:Palmitates; D013228:Stearates
keywords: inflammation; innate immunity; interleukin-1beta; linoleate; obesity; oleate; palmitate; stearate