The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2
ObjectiveIn this study, we mainly explored the mechanism and target of the anti-inflammatory effects of Aureusidin (Aur) in acute liver injury.MethodsLipopolysaccharide (LPS) was used to induce inflammatory injury in Kupffer cells (KCs) in vitro. After Aur treatment with gradient concentration, flow...
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Frontiers Media S.A.
2020
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oai:doaj.org-article:62ed104de7c54689b5290e01a02e2bf12021-12-03T13:31:51ZThe Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD21663-981210.3389/fphar.2020.570776https://doaj.org/article/62ed104de7c54689b5290e01a02e2bf12020-10-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2020.570776/fullhttps://doaj.org/toc/1663-9812ObjectiveIn this study, we mainly explored the mechanism and target of the anti-inflammatory effects of Aureusidin (Aur) in acute liver injury.MethodsLipopolysaccharide (LPS) was used to induce inflammatory injury in Kupffer cells (KCs) in vitro. After Aur treatment with gradient concentration, flow cytometry, propidium iodide (PI) staining, and Hoechst 33342 staining were used to detect the apoptotic level of KCs, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors, including Interleukin-1β (IL-1β), Interleukin-18 (IL-18), and tumor necrosis factor alpha (TNF-α). Western blot was used to detect the expression of toll-like receptor 4 (TLR4), myeloid differentiation protein-2 (MD2), MyD88, and p-P65. Aur was labeled with biotin, followed by a pull-down assay to detect its binding with MD2. Moreover, D-GalN/LPS was used to induce acute liver injury in mice in vitro, followed by Aur treatment by gavage. H&E staining was used to detect the pathological changes of liver tissue, an IF assay was used to detect the expression of MD2, Western blot was used to detect the expression of relevant proteins.ResultsAur pretreatment could significantly inhibit LPS-induced KC injury, downregulate the apoptotic level, inhibit the expression of inflammatory factors, decrease the level of MDA, and downregulate the expression of MD2 in cells. Aur could inhibit the activation level of TLR4/MD2-NF-κB in a dose-dependent pattern, a high dose of Aur had a superior effect compared to low-dose Aur. In the case of MD2 deletion, the effects of Aur were suppressed. Additionally, pull-down and co-immunoprecipitation assays show that Aur can bind with the MD2 protein to inhibit the activation of TLR4/MD2-NF-κB. Results of mice experiments also showed that Aur could relieve liver injury, decrease the levels of ALT and AST, and simultaneously downregulate the levels of inflammatory factors in tissues and peripheral blood.ConclusionWe found that Aur exerted an anti-inflammatory effect by directly targeting the MD2 protein, further inhibiting the expression of TLR4/MD2-NF-κB, thereby relieving acute liver injury. Therefore, Aur might be a potential inhibitor for MD2.Yi YangChenyang HanYongjia ShengJin WangXiaohong ZhouWenyan LiLi GuoShuiliang RuanFrontiers Media S.A.articleaureusidinmyeloiddifferentiation protein 2acute liver injuryinflammatory responselipopolysaccharidetoll likes receptorTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 11 (2020) |
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DOAJ |
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aureusidinmyeloid differentiation protein 2 acute liver injury inflammatory response lipopolysaccharide toll likes receptor Therapeutics. Pharmacology RM1-950 |
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aureusidinmyeloid differentiation protein 2 acute liver injury inflammatory response lipopolysaccharide toll likes receptor Therapeutics. Pharmacology RM1-950 Yi Yang Chenyang Han Yongjia Sheng Jin Wang Xiaohong Zhou Wenyan Li Li Guo Shuiliang Ruan The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| description |
ObjectiveIn this study, we mainly explored the mechanism and target of the anti-inflammatory effects of Aureusidin (Aur) in acute liver injury.MethodsLipopolysaccharide (LPS) was used to induce inflammatory injury in Kupffer cells (KCs) in vitro. After Aur treatment with gradient concentration, flow cytometry, propidium iodide (PI) staining, and Hoechst 33342 staining were used to detect the apoptotic level of KCs, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors, including Interleukin-1β (IL-1β), Interleukin-18 (IL-18), and tumor necrosis factor alpha (TNF-α). Western blot was used to detect the expression of toll-like receptor 4 (TLR4), myeloid differentiation protein-2 (MD2), MyD88, and p-P65. Aur was labeled with biotin, followed by a pull-down assay to detect its binding with MD2. Moreover, D-GalN/LPS was used to induce acute liver injury in mice in vitro, followed by Aur treatment by gavage. H&E staining was used to detect the pathological changes of liver tissue, an IF assay was used to detect the expression of MD2, Western blot was used to detect the expression of relevant proteins.ResultsAur pretreatment could significantly inhibit LPS-induced KC injury, downregulate the apoptotic level, inhibit the expression of inflammatory factors, decrease the level of MDA, and downregulate the expression of MD2 in cells. Aur could inhibit the activation level of TLR4/MD2-NF-κB in a dose-dependent pattern, a high dose of Aur had a superior effect compared to low-dose Aur. In the case of MD2 deletion, the effects of Aur were suppressed. Additionally, pull-down and co-immunoprecipitation assays show that Aur can bind with the MD2 protein to inhibit the activation of TLR4/MD2-NF-κB. Results of mice experiments also showed that Aur could relieve liver injury, decrease the levels of ALT and AST, and simultaneously downregulate the levels of inflammatory factors in tissues and peripheral blood.ConclusionWe found that Aur exerted an anti-inflammatory effect by directly targeting the MD2 protein, further inhibiting the expression of TLR4/MD2-NF-κB, thereby relieving acute liver injury. Therefore, Aur might be a potential inhibitor for MD2. |
| format |
article |
| author |
Yi Yang Chenyang Han Yongjia Sheng Jin Wang Xiaohong Zhou Wenyan Li Li Guo Shuiliang Ruan |
| author_facet |
Yi Yang Chenyang Han Yongjia Sheng Jin Wang Xiaohong Zhou Wenyan Li Li Guo Shuiliang Ruan |
| author_sort |
Yi Yang |
| title |
The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| title_short |
The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| title_full |
The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| title_fullStr |
The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| title_full_unstemmed |
The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver Injury by Regulating MD2 |
| title_sort |
mechanism of aureusidin in suppressing inflammatory response in acute liver injury by regulating md2 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2020 |
| url |
https://doaj.org/article/62ed104de7c54689b5290e01a02e2bf1 |
| work_keys_str_mv |
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