Lack of endogenous annexin A1 exacerbates NLRP3 inflammasome response in macrophages

José Marcos Sanches , Laura Branco, Sonia Oliani, Karina Bortoluci, Vanessa Moreira, Cristiane Gil

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Abstract

This study evalluated the role of endogenous Annexin A1 in the regulation of the
NLRP3 inflammasome. B57bl/6 wild-type (WT) and knockouts for ANXA1 (ANXA1-
/-) received intraperitoneal injection of 1.5% starch solution for macrophages
recruitment. NLRP3 was activated by priming cells with lipopolysaccharide (500
ng/mL) for 3 hours, followed by nigericin (10 µM for 1 hour) or ATP (5 mM for 30
minutes). After the treatments, the cells and supernatant were collected for ELISA,
western blotting, cell viability by MTT, ultrastructural immunocytochemistry
and, lipidomic analysis. As expected, nigericin and ATP administration decreased
macrophage viability, more pronounced in the ANXA1-/- cells, compared with
control and only LPS-treated cells (p < 0.001). Additionally, treatment with nigericin
and ATP produced a marked release of IL-1β in ANXA1-/- macrophages compared
to the other groups. Ultrastructural analysis demonstrated a high expression of
NLRP3 in the nigericin-activated ANXA1-/- macrophages. WT cells showed points of
co-localization of ANXA1 and NLRP3. Lipidomic analysis of macrophages evidenced
a completed different lipid profile between WT and ANXA1-/- supernatant cells.
In WT, nigericin administration induced a pronounced release of eicosanoids and
prostaglandins, while ANXA1-/- showed precursors of prostaglandin and some
ceramides. Altogether, our results suggested that endogenous ANXA1 regulates the
NLRP3-derived IL-1β in macrophages.
Original languageEnglish
Pages67
Publication statusPublished - 2019
Externally publishedYes
EventInternational Conference on Annexin Biology - Mûnster, Germany
Duration: 2019 Sept 152019 Sept 18
Conference number: 10th

Conference

ConferenceInternational Conference on Annexin Biology
Abbreviated titleANNEXINS
Country/TerritoryGermany
CityMûnster
Period2019/09/152019/09/18

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