TY  - JOUR
AU  - Lopes, Alexandre H.
AU  - Silva, Rangel L.
AU  - Fonseca, Miriam D.
AU  - Gomes, Francisco I.
AU  - Maganin, Alexandre G.
AU  - Secchim Ribeiro, Lucas
AU  - Marques, Lucas Maciel Mauriz
AU  - Cunha, Fernando Q.
AU  - Alves-Filho, Jose C.
AU  - Zamboni, Dario S.
AU  - Lopes, Norberto P.
AU  - Franklin, Bernardo S.
AU  - Gombault, Aurélie
AU  - Ramalho, Fernando Silva
AU  - Quesniaux, Valerie F. J.
AU  - Couillin, Isabelle
AU  - Ryffel, Bernhard
AU  - Cunha, Thiago M.
TI  - Molecular basis of carrageenan-induced cytokines production in macrophages
JO  - Cell communication and signaling
VL  - 18
IS  - 1
SN  - 1478-811X
CY  - London
PB  - Biomed Central
M1  - DZNE-2026-00092
SP  - 141
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Carrageenan: immunology
KW  - Cells, Cultured
KW  - Cytokines: immunology
KW  - Inflammasomes: immunology
KW  - Inflammation: immunology
KW  - Interleukin-1beta: immunology
KW  - Macrophage Activation
KW  - Macrophages, Peritoneal: immunology
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: immunology
KW  - Tumor Necrosis Factor-alpha: immunology
KW  - Carrageenan (Other)
KW  - IL-1β (Other)
KW  - Macrophages (Other)
KW  - NLRP3 Inflammasome (Other)
KW  - Pannexin-1 channel (Other)
KW  - Cytokines (NLM Chemicals)
KW  - IL1B protein, mouse (NLM Chemicals)
KW  - Inflammasomes (NLM Chemicals)
KW  - Interleukin-1beta (NLM Chemicals)
KW  - NLR Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals)
KW  - Nlrp3 protein, mouse (NLM Chemicals)
KW  - Tumor Necrosis Factor-alpha (NLM Chemicals)
KW  - Carrageenan (NLM Chemicals)
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1186/s12964-020-00621-x
UR  - https://pub.dzne.de/record/284084
ER  -