Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway
<b>Objective</b>: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Neverthe...
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MDPI AG
2023-03-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/3/534 |
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| author | Huiping Wu Ying Wang Haiyan Fu Lili Ji Na Li Dan Zhang Longxiang Su Zhansheng Hu |
| author_facet | Huiping Wu Ying Wang Haiyan Fu Lili Ji Na Li Dan Zhang Longxiang Su Zhansheng Hu |
| author_sort | Huiping Wu |
| collection | DOAJ |
| description | <b>Objective</b>: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Nevertheless, detailed functions and molecular mechanism of MaR1 in sepsis-induced cognitive dysfunction has not been fully elucidated. Here, we aimed to investigate potential neuroprotective effects of MaR1 on microglia-induced neuroinflammation in sepsis-induced cognitive impairment and to explore its anti-inflammatory mechanism. <b>Methods:</b> Different doses of MaR1 were administered to septic rats by via tail vein injection. The optimal dose was determined based on the 7-day survival rate of rats from each group. derived from macrophages with both anti-inflammatory to observe the ameliorative effects of MaR1 at optimal doses on cognitive dysfunction in septic rats. The effects of MaR1 on neuroinflammation-mediated microglial activation, neuronal apoptosis, and pro-inflammatory cytokine productions were in vivo and in vitro assayed, using Western blot, ELISA, TUNEL staining, Nissl staining, and the immunofluorescence method. To further elucidate anti-inflammatory machinery of MaR1, protein expressions of NLRP3 inflammatory vesicles and TLR4-NF-κB pathway-related proteins were subjected to Western blot assay. <b>Results:</b> After tail vein injection of MaR1 with different doses (2 ng/g, 4 ng/g, 8 ng/g), the results showed that 4 ng/g MaR1 treatment significantly increased the rats’ 7-day survival rate compared to the CLP controls. Therefore, subsequent experiments set 4 ng/g MaR1 as the optimal dose. Morris water maze experiments confirmed that MaR1 significantly reduced space memory dysfunction in rats. In addition, in CLP rats and LPS-stimulated BV2 microglia, MaR1 significantly reduced activated microglia and pro-inflammatory cytokines levels and neuronal apoptosis. Mechanically, MaR1 inhibits microglia-induced neuroinflammation through suppressing activations of NLRP3 inflammatory vesicles and TLR4-NF-κB signal pathway. <b>Conclusion:</b> Collectively, our findings suggested that MaR1 might be a prospective neuroprotective compound for prevention and treatment in the sepsis process. |
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| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T06:19:16Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-8264198261b94c1f9ae5fcad1f0123d72023-11-17T12:03:42ZengMDPI AGJournal of Personalized Medicine2075-44262023-03-0113353410.3390/jpm13030534Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling PathwayHuiping Wu0Ying Wang1Haiyan Fu2Lili Ji3Na Li4Dan Zhang5Longxiang Su6Zhansheng Hu7School of Medicine, Soochow University, Suzhou 215006, ChinaOperating Room, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, ChinaIntensive Care Unit, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, ChinaEmergency Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, ChinaIntensive Care Unit, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, ChinaIntensive Care Unit, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaSchool of Medicine, Soochow University, Suzhou 215006, China<b>Objective</b>: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Nevertheless, detailed functions and molecular mechanism of MaR1 in sepsis-induced cognitive dysfunction has not been fully elucidated. Here, we aimed to investigate potential neuroprotective effects of MaR1 on microglia-induced neuroinflammation in sepsis-induced cognitive impairment and to explore its anti-inflammatory mechanism. <b>Methods:</b> Different doses of MaR1 were administered to septic rats by via tail vein injection. The optimal dose was determined based on the 7-day survival rate of rats from each group. derived from macrophages with both anti-inflammatory to observe the ameliorative effects of MaR1 at optimal doses on cognitive dysfunction in septic rats. The effects of MaR1 on neuroinflammation-mediated microglial activation, neuronal apoptosis, and pro-inflammatory cytokine productions were in vivo and in vitro assayed, using Western blot, ELISA, TUNEL staining, Nissl staining, and the immunofluorescence method. To further elucidate anti-inflammatory machinery of MaR1, protein expressions of NLRP3 inflammatory vesicles and TLR4-NF-κB pathway-related proteins were subjected to Western blot assay. <b>Results:</b> After tail vein injection of MaR1 with different doses (2 ng/g, 4 ng/g, 8 ng/g), the results showed that 4 ng/g MaR1 treatment significantly increased the rats’ 7-day survival rate compared to the CLP controls. Therefore, subsequent experiments set 4 ng/g MaR1 as the optimal dose. Morris water maze experiments confirmed that MaR1 significantly reduced space memory dysfunction in rats. In addition, in CLP rats and LPS-stimulated BV2 microglia, MaR1 significantly reduced activated microglia and pro-inflammatory cytokines levels and neuronal apoptosis. Mechanically, MaR1 inhibits microglia-induced neuroinflammation through suppressing activations of NLRP3 inflammatory vesicles and TLR4-NF-κB signal pathway. <b>Conclusion:</b> Collectively, our findings suggested that MaR1 might be a prospective neuroprotective compound for prevention and treatment in the sepsis process.https://www.mdpi.com/2075-4426/13/3/534sepsismicrogliaMaresin1 (MaR1)TLR4-NF-κBNLRP3 inflammasome |
| spellingShingle | Huiping Wu Ying Wang Haiyan Fu Lili Ji Na Li Dan Zhang Longxiang Su Zhansheng Hu Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway Journal of Personalized Medicine sepsis microglia Maresin1 (MaR1) TLR4-NF-κB NLRP3 inflammasome |
| title | Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway |
| title_full | Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway |
| title_fullStr | Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway |
| title_full_unstemmed | Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway |
| title_short | Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway |
| title_sort | maresin1 ameliorates sepsis induced microglial neuritis induced through blocking tlr4 nf κ b nlrp3 signaling pathway |
| topic | sepsis microglia Maresin1 (MaR1) TLR4-NF-κB NLRP3 inflammasome |
| url | https://www.mdpi.com/2075-4426/13/3/534 |
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