دورية أكاديمية

Inhibition of TREM-1 alleviates neuroinflammation by modulating microglial polarization via SYK/p38MAPK signaling pathway after traumatic brain injury.

التفاصيل البيبلوغرافية
العنوان: Inhibition of TREM-1 alleviates neuroinflammation by modulating microglial polarization via SYK/p38MAPK signaling pathway after traumatic brain injury.
المؤلفون: Zhao T; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China., Zhou Y; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China., Zhang D; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China., Han D; Laboratory of Emergency Medicine, Second Clinical Medical College of Xuzhou Medical University, Xuzhou, Jiangsu, China; Xuzhou Key Laboratory of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China., Ma J; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China., Li S; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China., Li T; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China; School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: tingli8@xzhmu.edu.cn., Hu S; Laboratory of Emergency Medicine, Second Clinical Medical College of Xuzhou Medical University, Xuzhou, Jiangsu, China; Xuzhou Key Laboratory of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: hushuqun88@xzhmu.edu.cn., Li Z; Department of Forensic Science, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou, Jiangsu, China. Electronic address: lzhr@xzhmu.edu.cn.
المصدر: Brain research [Brain Res] 2024 Jul 01; Vol. 1834, pp. 148907. Date of Electronic Publication: 2024 Apr 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6240 (Electronic) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH: Brain Injuries, Traumatic*/metabolism , Brain Injuries, Traumatic*/drug therapy , Triggering Receptor Expressed on Myeloid Cells-1*/metabolism , Triggering Receptor Expressed on Myeloid Cells-1*/antagonists & inhibitors , Microglia*/metabolism , Microglia*/drug effects , Syk Kinase*/metabolism , Syk Kinase*/antagonists & inhibitors , Neuroinflammatory Diseases*/metabolism , Neuroinflammatory Diseases*/drug therapy , p38 Mitogen-Activated Protein Kinases*/metabolism, Animals ; Male ; Mice ; Signal Transduction/drug effects ; Brain Edema/metabolism ; Brain Edema/drug therapy ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/physiology ; Mice, Inbred C57BL
مستخلص: Background: Traumatic brain injury (TBI), as a major public health problem, is characterized by high incidence rate, disability rate, and mortality rate. Neuroinflammation plays a crucial role in the pathogenesis of TBI. Triggering receptor expressed on myeloid cells-1 (TREM-1) is recognized as an amplifier of the inflammation in diseases of the central nervous system (CNS). However, the function of TREM-1 remains unclear post-TBI. This study aimed to investigate the function of TREM-1 in neuroinflammation induced by TBI.
Methods: Brain water content (BWC), modified neurological severity score (mNSS), and Morris Water Maze (MWM) were measured to evaluate the effect of TREM-1 inhibition on nervous system function and outcome after TBI. TREM-1 expression in vivo was evaluated by Western blotting. The cellular localization of TREM-1 in the damaged region was observed via immunofluorescence staining. We also conducted Western blotting to examine expression of SYK, p-SYK and other downstream proteins.
Results: We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. It was further determined that TREM-1 was expressed on microglia and modulated subtype transition of microglia. Inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway.
Conclusions: These findings suggest that TREM-1 can be a potential clinical therapeutic target for alleviating neuroinflammation after TBI.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Microglia; Neuroinflammation; TREM-1; Traumatic brain injury (TBI); p38MAPK
المشرفين على المادة: 0 (Triggering Receptor Expressed on Myeloid Cells-1)
EC 2.7.10.2 (Syk Kinase)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
0 (TREM1 protein, mouse)
EC 2.7.10.2 (Syk protein, mouse)
تواريخ الأحداث: Date Created: 20240403 Date Completed: 20240509 Latest Revision: 20240611
رمز التحديث: 20240611
DOI: 10.1016/j.brainres.2024.148907
PMID: 38570153
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-6240
DOI:10.1016/j.brainres.2024.148907