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024 7 _ |a 10.1186/s12964-020-00621-x
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041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Lopes, Alexandre H.
|b 0
245 _ _ |a Molecular basis of carrageenan-induced cytokines production in macrophages
260 _ _ |a London
|c 2020
|b Biomed Central
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520 _ _ |a 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.
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588 _ _ |a Dataset connected to CrossRef, Journals: pub.dzne.de
650 _ 7 |a Carrageenan
|2 Other
650 _ 7 |a IL-1β
|2 Other
650 _ 7 |a Macrophages
|2 Other
650 _ 7 |a NLRP3 Inflammasome
|2 Other
650 _ 7 |a Pannexin-1 channel
|2 Other
650 _ 7 |a Cytokines
|2 NLM Chemicals
650 _ 7 |a IL1B protein, mouse
|2 NLM Chemicals
650 _ 7 |a Inflammasomes
|2 NLM Chemicals
650 _ 7 |a Interleukin-1beta
|2 NLM Chemicals
650 _ 7 |a NLR Family, Pyrin Domain-Containing 3 Protein
|2 NLM Chemicals
650 _ 7 |a Nlrp3 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Tumor Necrosis Factor-alpha
|2 NLM Chemicals
650 _ 7 |a Carrageenan
|0 9000-07-1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Carrageenan: immunology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Cytokines: immunology
|2 MeSH
650 _ 2 |a Inflammasomes: immunology
|2 MeSH
650 _ 2 |a Inflammation: immunology
|2 MeSH
650 _ 2 |a Interleukin-1beta: immunology
|2 MeSH
650 _ 2 |a Macrophage Activation
|2 MeSH
650 _ 2 |a Macrophages, Peritoneal: immunology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a NLR Family, Pyrin Domain-Containing 3 Protein: immunology
|2 MeSH
650 _ 2 |a Tumor Necrosis Factor-alpha: immunology
|2 MeSH
700 1 _ |a Silva, Rangel L.
|b 1
700 1 _ |a Fonseca, Miriam D.
|b 2
700 1 _ |a Gomes, Francisco I.
|b 3
700 1 _ |a Maganin, Alexandre G.
|b 4
700 1 _ |a Secchim Ribeiro, Lucas
|0 P:(DE-2719)9001782
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|u dzne
700 1 _ |a Marques, Lucas Maciel Mauriz
|b 6
700 1 _ |a Cunha, Fernando Q.
|b 7
700 1 _ |a Alves-Filho, Jose C.
|b 8
700 1 _ |a Zamboni, Dario S.
|b 9
700 1 _ |a Lopes, Norberto P.
|b 10
700 1 _ |a Franklin, Bernardo S.
|b 11
700 1 _ |a Gombault, Aurélie
|b 12
700 1 _ |a Ramalho, Fernando Silva
|b 13
700 1 _ |a Quesniaux, Valerie F. J.
|b 14
700 1 _ |a Couillin, Isabelle
|b 15
700 1 _ |a Ryffel, Bernhard
|b 16
700 1 _ |a Cunha, Thiago M.
|0 0000-0002-7855-3700
|b 17
773 _ _ |a 10.1186/s12964-020-00621-x
|g Vol. 18, no. 1, p. 141
|0 PERI:(DE-600)2126315-2
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|t Cell communication and signaling
|v 18
|y 2020
|x 1478-811X
856 4 _ |y OpenAccess
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