Molecular basis of carrageenan-induced cytokines production in macrophages

Background 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...

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Published in:Cell communication and signaling Vol. 18; no. 1; pp. 141 - 17
Main Authors: Lopes, Alexandre H., Silva, Rangel L., Fonseca, Miriam D., Gomes, Francisco I., Maganin, Alexandre G., Ribeiro, Lucas S., Marques, Lucas Maciel Mauriz, Cunha, Fernando Q., Alves-Filho, Jose C., Zamboni, Dario S., Lopes, Norberto P., Franklin, Bernardo S., Gombault, Aurélie, Ramalho, Fernando Silva, Quesniaux, Valerie F. J., Couillin, Isabelle, Ryffel, Bernhard, Cunha, Thiago M.
Format: Journal Article
Language:English
Published: London BioMed Central 07.09.2020
Springer Nature B.V
BMC
Subjects:
Antibodies
Biomedical and Life Sciences
Carrageenan
Cell activation
Cell Biology
Cell culture
Colitis
Cytokines
Cytokines and Growth Factors
Enzyme-linked immunosorbent assay
Gene expression
IL-1β
Immunofluorescence
Inflammasomes
Inflammation
Interleukin 1
Laboratories
Life Sciences
Macrophages
Molecular modelling
Molecular weight
MyD88 protein
NLRP3 Inflammasome
Pannexin-1 channel
Peritoneum
Polysaccharides
Protein-Ligand Interactions
Reactive oxygen species
Reagents
Receptors
Seaweeds
Signal transduction
Syk protein
TLR4 protein
Toll-like receptors
Tumor necrosis factor
Western blotting
NLRP3 Inflammasome
Pannexin-1 channel
Carrageenan
Macrophages
IL-1β
ISSN:1478-811X, 1478-811X
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Summary:Background 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. Methods 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 . Results 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. Conclusions 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. 1e-L4pWBc1sacKrQDF6Cf5 Video abstract Graphical 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.
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ISSN:1478-811X
1478-811X
DOI:10.1186/s12964-020-00621-x