Molecular mechanism of action responsible for carrageenan-induced inflammatory response

Myers, Michael J.; Deaver, Christine M.; Lewandowski, Anne

doi:10.1016/j.molimm.2019.02.020

Cited by 44 publications

(40 citation statements)

References 20 publications

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“…Thus, both actions of RM33, observed in cell cultures, support anti-inflammatory properties of the compound in vivo against proinflammatory stimuli, such as LPS, Freund’s complete adjuvant and carrageenan [ 27 , 28 ]. Of importance, all the studied proinflammatory stimuli [ 45 , 46 , 47 ] use both TLR2 and TLR4 receptors, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Although the inhibition by RM33 of LPS-induced IL-8 in human whole blood cultures was small ( Table S9 ), the inhibition of IL-8 production could have a significance in the in vivo suppression of carrageenan-induced inflammation [ 28 ] by lowering neutrophil migration [ 50 ] to the site of inflammation. In the rat model of carrageenan-induced inflammation, IL-8 plays a major role [ 51 ] and the signaling pathway induced by carrageenan involves TLR4 [ 45 ], as in the case of LPS [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

et al. 2021

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Previous studies demonstrated strong anti-inflammatory properties of isoxazolo[5,4-e]-1,2,4-triazepine (RM33) in vivo. The aim of this investigation was to describe synthesis, determine physicochemical characteristics, evaluate biological activities in murine and human in vitro models, as well as to propose mechanism of action of the compound. The compound was devoid of cell toxicity up to 100 μg/mL against a reference A549 cell line. Likewise, RM33 did not induce apoptosis in these cells. The compound stimulated concanavalin A (ConA)-induced splenocyte proliferation but did not change the secondary humoral immune response in vitro to sheep erythrocytes. Nevertheless, a low suppressive effect was registered on lipopolysaccharide (LPS)-induced splenocyte proliferation and a stronger one on tumor necrosis factor alpha (TNFα) production by rat peritoneal cells. The analysis of signaling pathways elicited by RM33 in nonstimulated resident cells and cell lines revealed changes associated with cell activation. Most importantly, we demonstrated that RM33 enhanced production of cyclooxygenase 2 in LPS-stimulated splenocytes. Based on the previous and herein presented results, we conclude that RM33 is an efficient, nontoxic immune suppressor with prevailing anti-inflammatory action. Additionally, structural studies were carried out with the use of appropriate spectral techniques in order to unequivocally confirm the structure of the RM33 molecule. Unambiguous assignment of NMR chemical shifts of carbon atoms of RM33 was conducted thanks to full detailed analysis of 1H, 13C NMR spectra and their two-dimensional (2D) variants. Comparison between theoretically predicted chemical shifts and experimental ones was also carried out. Additionally, N-deuterated isotopologue of RM33 was synthesized to eliminate potentially disturbing frequencies (such as NH, NH2 deformation vibrations) in the carbonyl region of the IR (infrared) spectrum to confirm the presence of the carbonyl group.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

et al. 2021

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“…It can be classified as type kappa (κ), iota (ι) and lambda (λ) and others according to the different form of sulfate binding. In the carrageenan family, κ‐carrageenan (κ‐CAR) is widely used in the food industry as a major texturizing agent for its excellent solubility, water‐binding, thickening and gelling properties 17,18 . κ‐CAR consists of a repeating disaccharide unit of α(1→4)‐3,6‐anhydro‐ d ‐galactose and β(1→3)‐ d ‐galactose 19,20 .…”

Section: Introductionmentioning

confidence: 99%

“…In the carrageenan family, κ-carrageenan (κ-CAR) is widely used in the food industry as a major texturizing agent for its excellent solubility, water-binding, thickening and gelling properties. 17,18 κ-CAR consists of a repeating disaccharide unit of ⊍(1→4)-3,6-anhydro-D-galactose and ⊎(1→3)-D-galactose. 19,20 Gel strength and WHC of salts-soluble meat proteins can be increased by κ-CAR.…”

Section: Introductionmentioning

confidence: 99%

Effect of κ‐carrageenan addition on protein structure and gel properties of salted duck egg white

et al. 2020

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BACKGROUND Salted duck egg white (SDEW) is a major by‐product during salted egg yolk manufacturing. Due to the high salt concentration, SDEW has not been efficiently utilized. Moreover, functional properties of SDEW are altered by salt during pickling. To improve the functional properties, the effect of κ‐carrageenan (κ‐CAR) addition on the protein structure and gel properties of SDEW was investigated in this study. RESULTS The surface hydrophobicity and free sulfhydryl content of SDEW protein increased, while total sulfhydryl content decreased significantly with the addition of κ‐CAR (0.02–0.10%). Fourier‐transform infrared spectroscopy analysis revealed that the relative content of α‐helix and β‐turn decreased, β‐sheet and random coil increased, indicating the variation tendency of protein structure from order to disorder. As κ‐CAR addition increased, the texture profiles including hardness, gumminess, chewiness, springiness, cohesiveness and resilience of SDEW gel were all improved. Water holding capacity increased significantly by 32.33% in the presence of 0.10% κ‐CAR addition. The scanning electron microscopy indicated that the microstructure of SDEW/κ‐CAR mixed gel was more smooth and compact. CONCLUSION The results suggested that adding κ‐CAR can be an effective method to improve gel quality of SDEW. This study is expected to provide theoretical basis for modification of SDEW protein, as well as preparation of food ingredients with better gel properties from SDEW. © 2020 Society of Chemical Industry

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“…Despite the fact that CGNs have been widely used in food industries for decades, their safety is still a topic of discussion [1,12,13]. A large number of animal experiments have shown that CGNs, particularly low-molecular-weight (low-MW) CGNs, can induce and promote the inflammatory response and intestinal cancer [14][15][16][17][18][19][20][21][22][23][24][25][26]. Indeed, poligeenan, which is designated as a fraction of CGN with Mw < 100 kDa, has been considered to exert deleterious impacts on the host health and recognized as food contaminant [1].…”

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confidence: 99%

Carrageenan oligosaccharides and their degrading bacteria induce intestinal inflammation in germ-free mouse

Yin

et al. 2020

Preprint

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Background: Carrageenans (CGNs) are widely used in food and pharmaceutical industries. However, the safety of CGNs is still under debate, because degraded CGNs have been reported to promote an intestinal inflammatory response in animal models. Here, we studied the relationship among CGNs, human gut microbiota, and the host inflammatory response.Methods: TLC was selected for detecting the degradation of KCPs by human gut microbiota in vitro batch fermentation system. PCR-DGGE and real time PCR were used for studying bacterial community. ESI-MS was used for KCPs structure analysis. Hematoxylin-eosin staining (HE), immunohistochemistry (IHC) and RNA-seq were used to evaluated the KCPs on host inflammation response in germ-free mice.Results: Thin-layer chromatography (TLC) data showed that CGNs with a molecular weight (Mw) higher than 100 kDa are not degraded by human fecal microbiota, but low Mw CGNs with an Mw around ~4.5 kDa (KCOs) could be degraded by seven of eight human fecal microbiota samples. KCO degrading B. xylanisolvens was isolated from fecal samples, and PCR-DGGE profiling with band sequencing suggested that B. xylanisolvens was the key KCO degrader in the human gut. Two putative κ-carrageenase genes were identified in the genome sequence of B. xylanisolvens. However, their function on KCO degrading was not verified in vitro. And the sulfate group from KCO is not removed after in vitro degradation by human fecal microbiota, as shown by ESI-MS analysis. The effects of KCO and KCO degrading bacteria on the inflammatory response were investigated in germ-free mice. Increased numbers of P-P38-, CD3a-, and CD79a-positive cells were found in the colon and rectum in mice fed with KCO plus KCO degrading bacteria than in mice fed with only KCO or only B. xylanisolvens and E. coli, as shown by RNA-Seq analysis, HE staining, and IHC. Conclusion: Our data suggested that the presence of KCO degrading bacteria promote the pro-inflammatory effects of CGNs.

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Molecular mechanism of action responsible for carrageenan-induced inflammatory response

Cited by 44 publications

References 20 publications

Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

Effect of κ‐carrageenan addition on protein structure and gel properties of salted duck egg white

Carrageenan oligosaccharides and their degrading bacteria induce intestinal inflammation in germ-free mouse

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