Journal Article

DZNE-2026-00092

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular basis of carrageenan-induced cytokines production in macrophages

Lopes, A. H. ; Silva, R. L. ; Fonseca, M. D. ; Gomes, F. I. ; Maganin, A. G. ; Secchim Ribeiro, L.Extern* ; Marques, L. M. M. ; Cunha, F. Q. ; Alves-Filho, J. C. ; Zamboni, D. S. ; Lopes, N. P. ; Franklin, B. S. ; Gombault, A. ; Ramalho, F. S. ; Quesniaux, V. F. J. ; Couillin, I. ; Ryffel, B. ; Cunha, T. M.

2020
Biomed Central London

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Please use a persistent id in citations: doi:10.1186/s12964-020-00621-x

Abstract: 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.

Keyword(s): Animals (MeSH) ; Carrageenan: immunology (MeSH) ; Cells, Cultured (MeSH) ; Cytokines: immunology (MeSH) ; Inflammasomes: immunology (MeSH) ; Inflammation: immunology (MeSH) ; Interleukin-1beta: immunology (MeSH) ; Macrophage Activation (MeSH) ; Macrophages, Peritoneal: immunology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: immunology (MeSH) ; Tumor Necrosis Factor-alpha: immunology (MeSH) ; Carrageenan ; IL-1β ; Macrophages ; NLRP3 Inflammasome ; Pannexin-1 channel ; Cytokines ; IL1B protein, mouse ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse ; Tumor Necrosis Factor-alpha ; Carrageenan

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Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

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