sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway
Abstract Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study invest...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10973-8 |
| _version_ | 1817976298072440832 |
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| author | Li Lu Xuan Liu Juanhua Fu Jun Liang Yayi Hou Huan Dou |
| author_facet | Li Lu Xuan Liu Juanhua Fu Jun Liang Yayi Hou Huan Dou |
| author_sort | Li Lu |
| collection | DOAJ |
| description | Abstract Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions. |
| first_indexed | 2024-04-13T22:00:43Z |
| format | Article |
| id | doaj.art-f5f6bd88db7b45e4ac214dfafb064ebc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T22:00:43Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f5f6bd88db7b45e4ac214dfafb064ebc2022-12-22T02:28:06ZengNature PortfolioScientific Reports2045-23222022-04-0112111610.1038/s41598-022-10973-8sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathwayLi Lu0Xuan Liu1Juanhua Fu2Jun Liang3Yayi Hou4Huan Dou5The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing UniversityDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing UniversityAbstract Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions.https://doi.org/10.1038/s41598-022-10973-8 |
| spellingShingle | Li Lu Xuan Liu Juanhua Fu Jun Liang Yayi Hou Huan Dou sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway Scientific Reports |
| title | sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway |
| title_full | sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway |
| title_fullStr | sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway |
| title_full_unstemmed | sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway |
| title_short | sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway |
| title_sort | strem 1 promotes the phagocytic function of microglia to induce hippocampus damage via the pi3k akt signaling pathway |
| url | https://doi.org/10.1038/s41598-022-10973-8 |
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