دورية أكاديمية
Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis.
| العنوان: | Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis. |
|---|---|
| المؤلفون: | Chen KM; Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan., Lai SC; Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: shih@csmu.edu.tw. |
| المصدر: | Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi [J Microbiol Immunol Infect] 2024 Aug; Vol. 57 (4), pp. 647-659. Date of Electronic Publication: 2024 May 30. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: published by Elsevier for the Taiwan Society of Microbiology Country of Publication: England NLM ID: 100956211 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-9133 (Electronic) Linking ISSN: 16841182 NLM ISO Abbreviation: J Microbiol Immunol Infect Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Feb. 2010- : Oxford, England : published by Elsevier for the Taiwan Society of Microbiology Original Publication: Taipei, Taiwan : Chinese Society of Microbiology : Chinese Society of Immunology [and] : Infectious Diseases Society of the Republic of China, |
| مواضيع طبية MeSH: | Angiostrongylus cantonensis*/drug effects , Meningoencephalitis*/drug therapy , Meningoencephalitis*/parasitology , Strongylida Infections*/drug therapy , Chromones*/pharmacology , Chromones*/therapeutic use , Morpholines*/pharmacology , Morpholines*/therapeutic use, Animals ; Mice ; Signal Transduction/drug effects ; Male ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Blood-Brain Barrier/drug effects ; Disease Models, Animal ; Phosphatidylinositol 3-Kinases/metabolism ; Anthelmintics/therapeutic use ; Anthelmintics/pharmacology ; Matrix Metalloproteinase 9/metabolism ; Eosinophilia/drug therapy ; Drug Therapy, Combination ; Sulfonamides |
| مستخلص: | Background: Co-therapy with albendazole and steroid is commonly used in patients with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis infections. However, anthelminthics often worsen symptoms, possibly due to the inflammatory reaction to antigens released by dying worms. Therefore, the present study was to investigate the curative effects and probable mechanisms of the platelet-derived growth factor receptor-beta (PDGFR-β) inhibitor AG1296 (AG) and the phosphoinositide 3-kinase inhibitor (PI3K) LY294002 (LY) in A. cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis. Methods: Western blots were used to detect matrix protein degradation and the expressions of PDGFR-β/PI3K signaling pathway. The co-localization of PDGFR-β and vascular smooth muscle cells (VSMCs), and metalloproteinase-9 (MMP-9) and VSMCs on the blood vessels were measured by confocal laser scanning immunofluorescence microscopy. Sandwich enzyme-linked immunosorbent assays were used to test S100B, interleukin (IL)-6, and transforming growth factor beta in the cerebrospinal fluid to determine their possible roles in mouse resistance to A. cantonensis. Results: The results showed that AG and LY cotherapy decreased the MMP-9 activity and inflammatory reaction. Furthermore, S100B, IL-6 and eosinophil counts were reduced by inhibitor treatment. The localization of PDGFR-β and MMP-9 was observed in VSMCs. Furthermore, we showed that the degradation of the neurovascular matrix and blood-brain barrier permeability were reduced in the mouse brain. Conclusions: These findings demonstrate the potential of PDGFR-β inhibitor AG and PI3K inhibitor LY co-therapy as anti-A. cantonensis drug candidates through improved neurovascular unit dysfunction and reduced inflammatory response. Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2024. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Angiostrongylus cantonensis; MMP-9; Meningoencephalitis; PDGFR-β; Signaling pathway |
| المشرفين على المادة: | 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) 0 (Chromones) 0 (Morpholines) 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate) EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 0 (Anthelmintics) EC 3.4.24.35 (Matrix Metalloproteinase 9) 0 (Sulfonamides) |
| SCR Disease Name: | Angiostrongyliasis |
| تواريخ الأحداث: | Date Created: 20240605 Date Completed: 20240810 Latest Revision: 20240810 |
| رمز التحديث: | 20240812 |
| DOI: | 10.1016/j.jmii.2024.05.012 |
| PMID: | 38839542 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1995-9133 |
|---|---|
| DOI: | 10.1016/j.jmii.2024.05.012 |