Original Research ARTICLE
CD36 shunts eicosanoid metabolism to repress CD14 licensed interleukin-1β release and inflammation
- 1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil
- 2Departamento de Física e Química, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil
- 3Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil
- 4Departamento de Puericultura e Pediatria, Ribeirão Preto Medical School, University of São Paulo, Brazil
- 5Departamento de Clínica Médica, Ribeirão Preto Medical School, University of São Paulo, Brazil
- 6Departamento de Farmacologia, Ribeirão Preto Medical School, University of São Paulo, Brazil
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. In contrast, CD36 shunts eicosanoid metabolism towards 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.
Keywords: interleukin-1β, Leukotriene B4, Prostaglandin E2, cAMP, CD36 receptor, CD14 receptor, venom
Received: 16 Feb 2018;
Accepted: 10 Apr 2018.
Edited by:Tobias Schuerholz, Universitätsmedizin Rostock, Germany
Reviewed by:Valerio Chiurchiù, Università Campus Bio-Medico, Italy
Hugo C. Castro-Faria-Neto, Fundação Oswaldo Cruz (Fiocruz), Brazil
Copyright: © 2018 Zoccal, Gardinassi, Sorgi, Meirelles, Bordon, Glezer, Cupo, Matsuno, Bollela, Arantes, Guimaraes and Faccioli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Lúcia H. Faccioli, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Ribeirão Preto, Brazil, firstname.lastname@example.org