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 molecu...
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BMC
2020-09-01
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Series: | Cell Communication and Signaling |
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Online Access: | http://link.springer.com/article/10.1186/s12964-020-00621-x |
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author | Alexandre H. Lopes Rangel L. Silva Miriam D. Fonseca Francisco I. Gomes Alexandre G. Maganin Lucas S. Ribeiro Lucas Maciel Mauriz Marques Fernando Q. Cunha Jose C. Alves-Filho Dario S. Zamboni Norberto P. Lopes Bernardo S. Franklin Aurélie Gombault Fernando Silva Ramalho Valerie F. J. Quesniaux Isabelle Couillin Bernhard Ryffel Thiago M. Cunha |
author_facet | Alexandre H. Lopes Rangel L. Silva Miriam D. Fonseca Francisco I. Gomes Alexandre G. Maganin Lucas S. Ribeiro Lucas Maciel Mauriz Marques Fernando Q. Cunha Jose C. Alves-Filho Dario S. Zamboni Norberto P. Lopes Bernardo S. Franklin Aurélie Gombault Fernando Silva Ramalho Valerie F. J. Quesniaux Isabelle Couillin Bernhard Ryffel Thiago M. Cunha |
author_sort | Alexandre H. Lopes |
collection | DOAJ |
description | 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-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. 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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last_indexed | 2024-04-11T23:45:01Z |
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spelling | doaj.art-fe56c29d443545788d694f1ed8880f872022-12-22T03:56:42ZengBMCCell Communication and Signaling1478-811X2020-09-0118111710.1186/s12964-020-00621-xMolecular basis of carrageenan-induced cytokines production in macrophagesAlexandre H. Lopes0Rangel L. Silva1Miriam D. Fonseca2Francisco I. Gomes3Alexandre G. Maganin4Lucas S. Ribeiro5Lucas Maciel Mauriz Marques6Fernando Q. Cunha7Jose C. Alves-Filho8Dario S. Zamboni9Norberto P. Lopes10Bernardo S. Franklin11Aurélie Gombault12Fernando Silva Ramalho13Valerie F. J. Quesniaux14Isabelle Couillin15Bernhard Ryffel16Thiago M. Cunha17Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Institute of Innate Immunity, University Hospitals, University of BonnDepartment of Physics and Chemistry, University of São PauloDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São PauloDepartment of Physics and Chemistry, University of São PauloInstitute of Innate Immunity, University Hospitals, University of BonnUniversity of Orleans and CNRS, UMR7355 Experimental and Molecular ImmunologyDepartment of Pathology, School of Medicine of Ribeirão Preto, University of São PauloUniversity of Orleans and CNRS, UMR7355 Experimental and Molecular ImmunologyUniversity of Orleans and CNRS, UMR7355 Experimental and Molecular ImmunologyUniversity of Orleans and CNRS, UMR7355 Experimental and Molecular ImmunologyDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Center for Research in Inflammatory Diseases (CRID)Av. Bandeirantes 3900Abstract 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. 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.http://link.springer.com/article/10.1186/s12964-020-00621-xCarrageenanMacrophagesIL-1βNLRP3 InflammasomePannexin-1 channel |
spellingShingle | Alexandre H. Lopes Rangel L. Silva Miriam D. Fonseca Francisco I. Gomes Alexandre G. Maganin Lucas S. Ribeiro Lucas Maciel Mauriz Marques Fernando Q. Cunha Jose C. Alves-Filho Dario S. Zamboni Norberto P. Lopes Bernardo S. Franklin Aurélie Gombault Fernando Silva Ramalho Valerie F. J. Quesniaux Isabelle Couillin Bernhard Ryffel Thiago M. Cunha Molecular basis of carrageenan-induced cytokines production in macrophages Cell Communication and Signaling Carrageenan Macrophages IL-1β NLRP3 Inflammasome Pannexin-1 channel |
title | Molecular basis of carrageenan-induced cytokines production in macrophages |
title_full | Molecular basis of carrageenan-induced cytokines production in macrophages |
title_fullStr | Molecular basis of carrageenan-induced cytokines production in macrophages |
title_full_unstemmed | Molecular basis of carrageenan-induced cytokines production in macrophages |
title_short | Molecular basis of carrageenan-induced cytokines production in macrophages |
title_sort | molecular basis of carrageenan induced cytokines production in macrophages |
topic | Carrageenan Macrophages IL-1β NLRP3 Inflammasome Pannexin-1 channel |
url | http://link.springer.com/article/10.1186/s12964-020-00621-x |
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