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Molecular basis of carrageenan-induced cytokines production in macrophages

  • Lopes, Alexandre H.1
  • Silva, Rangel L.1
  • Fonseca, Miriam D.1
  • Gomes, Francisco I.1
  • Maganin, Alexandre G.1
  • Ribeiro, Lucas S.2
  • Marques, Lucas Maciel Mauriz3
  • Cunha, Fernando Q.1
  • Alves-Filho, Jose C.1
  • Zamboni, Dario S.4
  • Lopes, Norberto P.3
  • Franklin, Bernardo S.2
  • Gombault, Aurélie5
  • Ramalho, Fernando Silva3
  • Quesniaux, Valerie F. J.5
  • Couillin, Isabelle5
  • Ryffel, Bernhard5
  • Cunha, Thiago M.1
  • 1 University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 2 University Hospitals, University of Bonn, Bonn, 53127, Germany , Bonn (Germany)
  • 3 University of São Paulo, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 4 Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 5 UMR7355 Experimental and Molecular Immunology, Orleans, France , Orleans (France)
Published Article
Cell Communication and Signaling
BioMed Central
Publication Date
Sep 07, 2020
DOI: 10.1186/s12964-020-00621-x
Springer Nature


BackgroundLow molecular weight carrageenan (Cg) is a seaweed-derived sulfated polysaccharide widely used as inflammatory stimulus in preclinical studies. However, the molecular mechanisms of Cg-induced inflammation are not fully elucidated. The present study aimed to investigate the molecular basis involved in Cg-induced macrophages activation and cytokines production.MethodsPrimary culture of mouse peritoneal macrophages were stimulated with Kappa Cg. The supernatant and cell lysate were used for ELISA, western blotting, immunofluorescence. Cg-induced mouse colitis was also developed.ResultsHere we show that Cg activates peritoneal macrophages to produce pro-inflammatory cytokines such as TNF and IL-1β. While Cg-induced TNF production/secretion depends on TLR4/MyD88 signaling, the production of pro-IL-1β relies on TLR4/TRIF/SYK/reactive oxygen species (ROS) signaling pathway. The maturation of pro-IL1β into IL-1β is dependent on canonical NLRP3 inflammasome activation via Pannexin-1/P2X7/K+ efflux signaling. In vivo, Cg-induced colitis was reduced in mice in the absence of NLRP3 inflammasome components.ConclusionsIn conclusion, we unravel a critical role of the NLRP3 inflammasome in Cg-induced pro-inflammatory cytokines production and colitis, which is an important discovery on the pro-inflammatory properties of this sulfated polysaccharide for pre-clinical studies.1e-L4pWBc1sacKrQDF6Cf5Video abstractGraphical AbstractCarrageenan (Cg) is one the most used flogistic stimulus in preclinical studies. Nevertheless, the molecular basis of Cg-induced inflammation is not totally elucidated. Herein, Lopes et al. unraveled the molecular basis for Cg-induced macrophages production of biological active IL-1β. The Cg-stimulated macrophages produces pro-IL-1β depends on TLR4/TRIF/Syk/ROS, whereas its processing into mature IL-1β is dependent on the canonical NLRP3 inflammasome.

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