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@ARTICLE{Lopes:284084,
author = {Lopes, Alexandre H. and Silva, Rangel L. and Fonseca,
Miriam D. and Gomes, Francisco I. and Maganin, Alexandre G.
and Secchim Ribeiro, Lucas and Marques, Lucas Maciel Mauriz
and Cunha, Fernando Q. and Alves-Filho, Jose C. and Zamboni,
Dario S. and Lopes, Norberto P. and Franklin, Bernardo S.
and Gombault, Aurélie and Ramalho, Fernando Silva and
Quesniaux, Valerie F. J. and Couillin, Isabelle and Ryffel,
Bernhard and Cunha, Thiago M.},
title = {{M}olecular basis of carrageenan-induced cytokines
production in macrophages},
journal = {Cell communication and signaling},
volume = {18},
number = {1},
issn = {1478-811X},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2026-00092},
pages = {141},
year = {2020},
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.},
keywords = {Animals / Carrageenan: immunology / Cells, Cultured /
Cytokines: immunology / Inflammasomes: immunology /
Inflammation: immunology / Interleukin-1beta: immunology /
Macrophage Activation / Macrophages, Peritoneal: immunology
/ Male / Mice / Mice, Inbred C57BL / NLR Family, Pyrin
Domain-Containing 3 Protein: immunology / Tumor Necrosis
Factor-alpha: immunology / Carrageenan (Other) / IL-1β
(Other) / Macrophages (Other) / NLRP3 Inflammasome (Other) /
Pannexin-1 channel (Other) / Cytokines (NLM Chemicals) /
IL1B protein, mouse (NLM Chemicals) / Inflammasomes (NLM
Chemicals) / Interleukin-1beta (NLM Chemicals) / NLR Family,
Pyrin Domain-Containing 3 Protein (NLM Chemicals) / Nlrp3
protein, mouse (NLM Chemicals) / Tumor Necrosis Factor-alpha
(NLM Chemicals) / Carrageenan (NLM Chemicals)},
ddc = {570},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1186/s12964-020-00621-x},
url = {https://pub.dzne.de/record/284084},
}