Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB, AP‐1, and MAPKs signaling

Park, Jun-Young; Kwak, Choong Hwan; Ha, Sun-Hyung; Kwon, Kyung-Min; Abekura, Fukushi; Cho, Seung-Hak; Chang, Young‐Chae; Lee, Young Choon; Ha, Ki‐Tae; Chung, Tae‐Wook; Kim, Cheorl-Ho

doi:10.1002/jcb.26287

Cited by 35 publications

(22 citation statements)

References 40 publications

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“…The NFκB is then phosphorylated and converted to its active form. In the NFκB signaling pathway, MAPK regulates the activation of NFκB; the phosphorylation of MAPK induces the activation of NFκB followed by subsequent expression of inflammatory mediators and pro-inflammatory cytokines [ 10 , 22 ]. To investigate the effect of atraric acid on the MAPK/NFκB signaling pathway, LPS-stimulated RAW264.7 cells were treated with atraric acid to analyze the expression of the inflammatory mediators by Western blot.…”

Section: Resultsmentioning

confidence: 99%

“…In the LPS stimulated inflammation, toll-like receptor-4 (TLR4) and MD-2 in macrophages form heterodimers that recognize common patterns of an LPS molecule [ 26 ]. Upstream signaling initiated from the interaction of LPS and TLR4 complex induced the activation of MAPKs/NFκB signaling pathway, which results in overexpression of inflammatory factors [ 22 ]. The overexpression of the inflammatory factors, such as enzymes iNOS and COX-2 and pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β, induces cellular inflammatory responses and consequently leads to in vivo damage such as endotoxin shock ( Figure 8 ) [ 6 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

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Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

Mun

Kang²,

Jang³

et al. 2020

IJMS

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Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite atraric acid produced by Heterodermia hypoleuca. The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

Mun

Kang²,

Jang³

et al. 2020

IJMS

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“…Previous studies indicated that several gangliosides, such as GM3 and GD1a, trigger anti-inflammatory responses in LPS-stimulated RAW264.7 macrophages [ 43 , 44 ]. In the present study, we provided evidence that Hp-s1 had an anti-neuroinflammatory role in LPS-stimulated microglial cells.…”

Section: Discussionmentioning

confidence: 99%

Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

Shih

Tsai

et al. 2020

Marine Drugs

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Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.

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“…Recent findings suggest that tumor-shed ganglioside is a secretory factor regulating the phenotype of macrophages and consequently enhancing angiogenesis [12]. In addition, exogenous GM3 ganglioside can suppress the lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cell line [13]. In macrophages and microglia, the ganglioside content available in the extracellular space modulates Toll-like receptor 4 (TLR4) mediated stimulation [14,15].…”

Section: Introductionmentioning

confidence: 99%

Ganglioside Synthesis by Plasma Membrane-Associated Sialyltransferase in Macrophages

Vilcaes

Garbarino-Pico

Demichelis

et al. 2020

IJMS

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Gangliosides are constituents of the mammalian cell membranes and participate in the inflammatory response. However, little is known about the presence and enzymatic activity of ganglioside sialyltransferases at the cell surface of macrophages, one of the most important immune cells involved in the innate inflammatory process. In the present study, using biochemical and fluorescent microscopy approaches, we found that endogenous ST8Sia-I is present at the plasma membrane (ecto-ST8Sia-I) of murine macrophage RAW264.7 cells. Moreover, ecto-ST8Sia-I can synthetize GD3 ganglioside at the cell surface in lipopolysaccharide (LPS)-stimulated macrophages even when LPS-stimulated macrophages reduced the total ST8Sia-I expression levels. Besides, cotreatment of LPS with an inhibitor of nitric oxide (NO) synthase recovered the ecto-ST8Sia-I expression, suggesting that NO production is involved in the reduction of ST8Sia-I expression. The diminution of ST8Sia-I expression in LPS-stimulated macrophages correlated with a reduction of GD3 and GM1 gangliosides and with an increment of GD1a. Taken together, the data supports the presence and activity of sialyltransferases at the plasma membrane of RAW264.7 cells. The variations of ecto-ST8Sia-I and ganglioside levels in stimulated macrophages constitutes a promissory pathway to further explore the physiological role of this and others ganglioside metabolism-related enzymes at the cell surface during the immune response.

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Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB, AP‐1, and MAPKs signaling

Cited by 35 publications

References 40 publications

Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

Ganglioside Synthesis by Plasma Membrane-Associated Sialyltransferase in Macrophages

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