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-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. 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.

Effects of E407a on the viability, metabolic and functional activity of dermal fibroblasts

“…It has been reported that carrageenan toxicity is mediated by the TLR4-and NF-kB-associated pathways, NLRP3 inflammasome pathway, ROS-mediated damage and, hence, upregulation of pro-inflammatory cytokines [25,[29][30][31]. The role of pathways outlined above in immune cells is more pronounced compared with fibroblasts, which can be speculated to explain the difference in cytotoxic effects of semi-refined carrageenan on different types of cells.…”

Analgesic and anti-inflammatory potential of Lupeol isolated from Indian traditional medicinal plant Crateva adansonii screened through in vivo and in silico approaches

“…Carrageenan is a sulfated polysaccharide substance used to produce inflammatory immune response in experimental animals leading to the release of pro-inflammatory mediators such as prostaglandin, histamine, bradykinin, leukotrienes, etc. [30]. The mechanism of carrageenan-induced inflammation in two-phase response, serotonin, and histamine released during the first phase followed by the release of prostaglandins, lysosome enzymes during the second phase [31][32][33].…”

Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway

“…The inflammatory response happens through the interaction of either pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns with pattern recognition receptors [ 1 , 4 ]. For instance, engagement of PAMPs such as gram-negative bacteria-derived lipopolysaccharides (LPS) or carrageenan into toll-like receptor 4 will induce recruitment of adaptor proteins, MyD88 and TRIF, into the cytoplasm that eventually triggers inflammatory signaling cascades, including the activator protein-1 (AP-1) pathway [ 2 , 5 , 6 ]. The activation of the inflammatory signaling pathway is mediated by the initiation of signal transduction cascades activating a variety of intracellular signaling molecules.…”