CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

Frontiers in Immunology
Karina Furlani ZoccalLúcia Helena Faccioli

Abstract

Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus. In this context, bioactive lipids such as prostaglandin (PG)E2 and leukotriene (LT)B4 modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB4, PGE2, and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE2/cAMP/IL-1β release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB4, which represses the PGE2/cAMP/IL-1β axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1β.

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Citations

Nov 23, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Priscilla A T PereiraLúcia H Faccioli
Mar 20, 2019·Frontiers in Pharmacology·Karina F ZoccalLúcia H Faccioli
Aug 1, 2019·Medicines·Bruno A C NascimentoKarina F Zoccal
Oct 18, 2019·Frontiers in Immunology·Péricles Gama Abreu-FilhoAdriana Malheiro
Apr 4, 2021·International Journal of Molecular Sciences·Nina ĐukanovićZoran Todorović
May 4, 2021·Frontiers in Immunology·Felipe Silva de FrançaDenise V Tambourgi
May 28, 2021·Frontiers in Immunology·Rachael Y M RyanJohn J Miles

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Methods Mentioned

BETA
Flow Cytometry
density gradient centrifugation
genotyping
PCR
enzyme-linked immunosorbent assay
Protein Assay
acetylation

Software Mentioned

GraphPad Prism
Leica QWin
FlowJo

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