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000284084 1001_ $$aLopes, Alexandre H.$$b0
000284084 245__ $$aMolecular basis of carrageenan-induced cytokines production in macrophages
000284084 260__ $$aLondon$$bBiomed Central$$c2020
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000284084 520__ $$aLow molecular weight carrageenan (Cg) is a seaweed-derived sulfated polysaccharide widely used as inflammatory stimulus in preclinical studies. However, the molecular mechanisms of Cg-induced inflammation are not fully elucidated. The present study aimed to investigate the molecular basis involved in Cg-induced macrophages activation and cytokines production.Primary culture of mouse peritoneal macrophages were stimulated with Kappa Cg. The supernatant and cell lysate were used for ELISA, western blotting, immunofluorescence. Cg-induced mouse colitis was also developed.Here we show that Cg activates peritoneal macrophages to produce pro-inflammatory cytokines such as TNF and IL-1β. While Cg-induced TNF production/secretion depends on TLR4/MyD88 signaling, the production of pro-IL-1β relies on TLR4/TRIF/SYK/reactive oxygen species (ROS) signaling pathway. The maturation of pro-IL1β into IL-1β is dependent on canonical NLRP3 inflammasome activation via Pannexin-1/P2X7/K+ efflux signaling. In vivo, Cg-induced colitis was reduced in mice in the absence of NLRP3 inflammasome components.In conclusion, we unravel a critical role of the NLRP3 inflammasome in Cg-induced pro-inflammatory cytokines production and colitis, which is an important discovery on the pro-inflammatory properties of this sulfated polysaccharide for pre-clinical studies. Video abstract Carrageenan (Cg) is one the most used flogistic stimulus in preclinical studies. Nevertheless, the molecular basis of Cg-induced inflammation is not totally elucidated. Herein, Lopes et al. unraveled the molecular basis for Cg-induced macrophages production of biological active IL-1β. The Cg-stimulated macrophages produces pro-IL-1β depends on TLR4/TRIF/Syk/ROS, whereas its processing into mature IL-1β is dependent on the canonical NLRP3 inflammasome.
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000284084 650_7 $$2Other$$aCarrageenan
000284084 650_7 $$2Other$$aIL-1β
000284084 650_7 $$2Other$$aMacrophages
000284084 650_7 $$2Other$$aNLRP3 Inflammasome
000284084 650_7 $$2Other$$aPannexin-1 channel
000284084 650_7 $$2NLM Chemicals$$aCytokines
000284084 650_7 $$2NLM Chemicals$$aIL1B protein, mouse
000284084 650_7 $$2NLM Chemicals$$aInflammasomes
000284084 650_7 $$2NLM Chemicals$$aInterleukin-1beta
000284084 650_7 $$2NLM Chemicals$$aNLR Family, Pyrin Domain-Containing 3 Protein
000284084 650_7 $$2NLM Chemicals$$aNlrp3 protein, mouse
000284084 650_7 $$2NLM Chemicals$$aTumor Necrosis Factor-alpha
000284084 650_7 $$09000-07-1$$2NLM Chemicals$$aCarrageenan
000284084 650_2 $$2MeSH$$aAnimals
000284084 650_2 $$2MeSH$$aCarrageenan: immunology
000284084 650_2 $$2MeSH$$aCells, Cultured
000284084 650_2 $$2MeSH$$aCytokines: immunology
000284084 650_2 $$2MeSH$$aInflammasomes: immunology
000284084 650_2 $$2MeSH$$aInflammation: immunology
000284084 650_2 $$2MeSH$$aInterleukin-1beta: immunology
000284084 650_2 $$2MeSH$$aMacrophage Activation
000284084 650_2 $$2MeSH$$aMacrophages, Peritoneal: immunology
000284084 650_2 $$2MeSH$$aMale
000284084 650_2 $$2MeSH$$aMice
000284084 650_2 $$2MeSH$$aMice, Inbred C57BL
000284084 650_2 $$2MeSH$$aNLR Family, Pyrin Domain-Containing 3 Protein: immunology
000284084 650_2 $$2MeSH$$aTumor Necrosis Factor-alpha: immunology
000284084 7001_ $$aSilva, Rangel L.$$b1
000284084 7001_ $$aFonseca, Miriam D.$$b2
000284084 7001_ $$aGomes, Francisco I.$$b3
000284084 7001_ $$aMaganin, Alexandre G.$$b4
000284084 7001_ $$0P:(DE-2719)9001782$$aSecchim Ribeiro, Lucas$$b5$$udzne
000284084 7001_ $$aMarques, Lucas Maciel Mauriz$$b6
000284084 7001_ $$aCunha, Fernando Q.$$b7
000284084 7001_ $$aAlves-Filho, Jose C.$$b8
000284084 7001_ $$aZamboni, Dario S.$$b9
000284084 7001_ $$aLopes, Norberto P.$$b10
000284084 7001_ $$aFranklin, Bernardo S.$$b11
000284084 7001_ $$aGombault, Aurélie$$b12
000284084 7001_ $$aRamalho, Fernando Silva$$b13
000284084 7001_ $$aQuesniaux, Valerie F. J.$$b14
000284084 7001_ $$aCouillin, Isabelle$$b15
000284084 7001_ $$aRyffel, Bernhard$$b16
000284084 7001_ $$00000-0002-7855-3700$$aCunha, Thiago M.$$b17
000284084 773__ $$0PERI:(DE-600)2126315-2$$a10.1186/s12964-020-00621-x$$gVol. 18, no. 1, p. 141$$n1$$p141$$tCell communication and signaling$$v18$$x1478-811X$$y2020
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