%0 Journal Article
%A Lopes, Alexandre H.
%A Silva, Rangel L.
%A Fonseca, Miriam D.
%A Gomes, Francisco I.
%A Maganin, Alexandre G.
%A Secchim Ribeiro, Lucas
%A Marques, Lucas Maciel Mauriz
%A Cunha, Fernando Q.
%A Alves-Filho, Jose C.
%A Zamboni, Dario S.
%A Lopes, Norberto P.
%A Franklin, Bernardo S.
%A Gombault, Aurélie
%A Ramalho, Fernando Silva
%A Quesniaux, Valerie F. J.
%A Couillin, Isabelle
%A Ryffel, Bernhard
%A Cunha, Thiago M.
%T Molecular basis of carrageenan-induced cytokines production in macrophages
%J Cell communication and signaling
%V 18
%N 1
%@ 1478-811X
%C London
%I Biomed Central
%M DZNE-2026-00092
%P 141
%D 2020
%X Low 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.Primary 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.Here 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.In 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. Video abstract Carrageenan (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.
%K Animals
%K Carrageenan: immunology
%K Cells, Cultured
%K Cytokines: immunology
%K Inflammasomes: immunology
%K Inflammation: immunology
%K Interleukin-1beta: immunology
%K Macrophage Activation
%K Macrophages, Peritoneal: immunology
%K Male
%K Mice
%K Mice, Inbred C57BL
%K NLR Family, Pyrin Domain-Containing 3 Protein: immunology
%K Tumor Necrosis Factor-alpha: immunology
%K Carrageenan (Other)
%K IL-1β (Other)
%K Macrophages (Other)
%K NLRP3 Inflammasome (Other)
%K Pannexin-1 channel (Other)
%K Cytokines (NLM Chemicals)
%K IL1B protein, mouse (NLM Chemicals)
%K Inflammasomes (NLM Chemicals)
%K Interleukin-1beta (NLM Chemicals)
%K NLR Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals)
%K Nlrp3 protein, mouse (NLM Chemicals)
%K Tumor Necrosis Factor-alpha (NLM Chemicals)
%K Carrageenan (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1186/s12964-020-00621-x
%U https://pub.dzne.de/record/284084