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Carrageenan Triggers NLRP3 Inflammasome Activation and IL-1β Production by Macrophages

39 Pages Posted: 20 Jun 2019

See all articles by Alexandre H. Lopes

Alexandre H. Lopes

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Rangel L. Silva

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Miriam D. Fonseca

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Francisco I. Gomes

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Alexandre G. Maganin

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Lucas S. Ribeiro

University of Bonn - Institute of Innate Immunity

Fernando Q. Cunha

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Jose C. Alves-Filho

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Dario S. Zamboni

University of São Paulo (USP)

Bernardo S. Franklin

University of Bonn - Institute of Innate Immunity

Aurélie Gombault

University of Orleans

Valerie FJ Quesniaux

University of Orleans

Isabelle Couillin

University of Orleans

Bernhard Ryffel

University of Orleans

Thiago Cunha

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

More...

Abstract

Background: Carrageenan (Cg) is a seaweed-derived sulfated polysaccharide widely used as a food additive with the inflammatory property. However, the molecular mechanisms of Cg-induced inflammation are not fully elucidated. The present study aimed to investigate the IL-1β production depends on TLR4/TRIF cascade and subsequent NLRP3 inflammasome activation.

Methods: The undergoing mechanisms in which Cg-mediated macrophages activation were determined by ELISA, Pharmacological approachs and immunolabeling assay. The expression of IL-1β and caspase-1 activity were examined by quantitative PCR and western blotting analyses. The in vivo effect of Cg was investigated in a model of colitis.

Findings: 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 Pannexin1/P2X7/K+ efflux signaling. In vivo, Cg-induced colitis was reduced in mice in the absence of NLRP3 inflammasome.

Interpretation: We unravel a critical role of the NLRP3 inflammasome in Cg-induced IL-1β secretion and colitis, which is an important discovery on the pro-inflammatory properties of this sulfated polysaccharide for pre-clinical studies and potential undesired effects used as a food additive.

Funding: The research leading to these results received funding from São Paulo Research Foundation (FAPESP) under grant agreements n° 2013/08216-2 (Center for Research in Inflammatory Disease) and 2011/19670-0 (Thematic Project), CNPq n. 141150/2013-0, and from Centre National de la Recherche Scientifique (CNRS) and European Regional Development Fund (FEDER n°2016-00110366).

Declaration of Interests: All authors declare no Conflict of Interest.

Ethics Approval Statement: Animal care and handling procedures were in accordance with Ethics Committee on Animal Experimentation of the Ribeirão Preto Medical School, University of São Paulo. Approval for ethical animal care and use was obtained before the beginning of this study (Process nº 180/2016).

Keywords: Carrageenan, Macrophages, IL-1β, NLRP3 Inflammasome, Pannexin-1 channel

Suggested Citation

Lopes, Alexandre H. and Silva, Rangel L. and Fonseca, Miriam D. and Gomes, Francisco I. and Maganin, Alexandre G. and Ribeiro, Lucas S. and Cunha, Fernando Q. and Alves-Filho, Jose C. and Zamboni, Dario S. and Franklin, Bernardo S. and Gombault, Aurélie and Quesniaux, Valerie FJ and Couillin, Isabelle and Ryffel, Bernhard and Cunha, Thiago, Carrageenan Triggers NLRP3 Inflammasome Activation and IL-1β Production by Macrophages (June 17, 2019). Available at SSRN: https://ssrn.com/abstract=3405570

Alexandre H. Lopes

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Rangel L. Silva

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Miriam D. Fonseca

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Francisco I. Gomes

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Alexandre G. Maganin

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Lucas S. Ribeiro

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Fernando Q. Cunha

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Jose C. Alves-Filho

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID)

Brazil

Dario S. Zamboni

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Bernardo S. Franklin

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Aurélie Gombault

University of Orleans

Rue de Blois
B.P. 6739
45067 Orleans Cedex 2, Orleans cedex 2 45067
France

Valerie FJ Quesniaux

University of Orleans

Rue de Blois
B.P. 6739
45067 Orleans Cedex 2, Orleans cedex 2 45067
France

Isabelle Couillin

University of Orleans

Rue de Blois
B.P. 6739
45067 Orleans Cedex 2, Orleans cedex 2 45067
France

Bernhard Ryffel

University of Orleans

Rue de Blois
B.P. 6739
45067 Orleans Cedex 2, Orleans cedex 2 45067
France

Thiago Cunha (Contact Author)

University of São Paulo (USP) - Center for Research in Inflammatory Diseases (CRID) ( email )

Brazil

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