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Lipin-2 inhibits inflammasome activation induced by palmitic acid in macrophages

AuthorsSanjuán-García, Itziar; Balsinde, Jesús ; Balboa, María A.
Issue Date2016
CitationCIBERDEM Annual Meeting (2016)
AbstractIt is well known that metabolic diseases are characterized by elevated concentrations of circulating free fatty acids (FFAs), especially saturated fatty acids (SFAs), which activate macrophages through Toll-like receptors (TLR2/4). Previous studies in our laboratory showed that depletion of lipin-2, a member of the phosphatidic acid phosphatase lipin family involved in de novo lipid biosynthesis, promotes increased an inflammatory response to SFAs such as palmitic acid. Further studies demonstrated that this inflammatory response also involves the increased expression and release of IL-1b, a pro-inflammatory cytokine produced by the activation of the NLRP3 (NLR pyrin domain containing 3) inflammasome. The aim of this study was to further investigate the mechanism by which the lack of lipin-2 increases the inflammasome-dependent response to palmitic acid. We produced a human macrophage cell line (THP1) knockout for lipin-2 using the CRISPR/Cas9 technology by lentiviral transfection. Palmitic acid has the capacity to act as the first and second signal needed to fully activate the NLRP3 inflammasome. During the priming signal (signal 1) palmitic acid induces proinflammatory gene expression (Il1b, Il6) by activating via ERK and NFKB, possibly through TLR2/4. As signal 2, the fatty acid induces the formation of the NLRP3 inflammasome complex and activation of caspase-1, with the consequent maturation of pro-IL-1b into IL-1b. Lipin-2 depletion has effects on the priming phase of the inflammasome activation, by increasing p65 NF-Kb translocation to the nucleus as well as activation of ERK. During the second phase, the absence of lipin-2 exacerbates palmitic acid-inflammasome activation, increasing expression of pro-IL-1b and components of the NLRP3 inflammasome complex. Collectively, these data suggest that lipin-2 participates as a mechanism to dampen inflammasome activation during palmitic acid treatment. We are currently working to characterize the molecular mechanisms that govern these effects.
DescriptionResumen del póster presentado presentado al CIBERDEM Annual Meeting, celebrado en Cerdanyola del Vallès, Barcelona (España) del 11 al 13 de mayo de 2016.
Appears in Collections:(IBGM) Comunicaciones congresos
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