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Molecular basis of carrageenan-induced cytokines production in macrophages.

ABSTRACT: 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-1?. While Cg-induced TNF production/secretion depends on TLR4/MyD88 signaling, the production of pro-IL-1? relies on TLR4/TRIF/SYK/reactive oxygen species (ROS) signaling pathway. The maturation of pro-IL1? into IL-1? 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. 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-1?. The Cg-stimulated macrophages produces pro-IL-1? depends on TLR4/TRIF/Syk/ROS, whereas its processing into mature IL-1? is dependent on the canonical NLRP3 inflammasome.

SUBMITTER: Lopes AH

PROVIDER: S-EPMC7487827 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Molecular basis of carrageenan-induced cytokines production in macrophages.

Lopes Alexandre H AH Silva Rangel L RL Fonseca Miriam D MD Gomes Francisco I FI Maganin Alexandre G AG Ribeiro Lucas S LS Marques Lucas Maciel Mauriz LMM Cunha Fernando Q FQ Alves-Filho Jose C JC Zamboni Dario S DS Lopes Norberto P NP Franklin Bernardo S BS Gombault Aurélie A Ramalho Fernando Silva FS Quesniaux Valerie F J VFJ Couillin Isabelle I Ryffel Bernhard B Cunha Thiago M TM

Cell communication and signaling : CCS 20200907 1

<h4>Background</h4>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.<h4>Methods</h4>Primary culture of mouse peritoneal macrophages were stimulated with Kappa Cg. The supernatant and cell ...[more]

PMID: 32894139

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Dataset Information

Molecular basis of carrageenan-induced cytokines production in macrophages.

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Molecular basis of carrageenan-induced cytokines production in macrophages.

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