دورية أكاديمية
Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCβ1 signaling pathway in diabetic atherosclerosis
| العنوان: | Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCβ1 signaling pathway in diabetic atherosclerosis |
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| المؤلفون: | Liding Zhao, Ya Li, Tian Xu, Qingbo Lv, Xukun Bi, Xianglan Liu, Guosheng Fu, Yunzeng Zou, Junbo Ge, Zhaoyang Chen, Wenbin Zhang |
| المصدر: | Molecular Medicine, Vol 28, Iss 1, Pp 1-17 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Biochemistry |
| مصطلحات موضوعية: | Atherosclerosis, Diabetes, Inflammation, Dendritic cells, Protein Kinase C, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436 |
| الوصف: | Abstract Background The unique mechanism of diabetic atherosclerosis has been a central research focus. Previous literature has reported that the inflammatory response mediated by dendritic cells (DCs) plays a vital role in the progression of atherosclerosis. The objective of the study was to explore the role of DCs in diabetes mellitus complicated by atherosclerosis. Methods ApoE−/− mice and bone marrow-derived DCs were used for in vivo and in vitro experiments, respectively. Masson’s staining and Oil-red-O staining were performed for atherosclerotic lesion assessment. The content of macrophages and DCs in plaque was visualized by immunohistochemistry. The expression of CD83 and CD86 were detected by flow cytometry. The fluctuations in the RNA levels of cytokines, chemokines, chemokine receptors and adhesions were analyzed by quantitative RT-PCR. The concentrations of IFN-γ and TNF-α were calculated using ELISA kits and the proteins were detected using western blot. Coimmunoprecipitation was used to detect protein–protein interactions. Results Compared with the ApoE−/− group, the volume of atherosclerotic plaques in the aortic root of diabetic ApoE−/− mice was significantly increased, numbers of macrophages and DCs were increased, and the collagen content in plaques decreased. The expression of CD83 and CD86 were significantly upregulated in splenic CD11c+ DCs derived from mice with hyperglycemia. Increased secretion of cytokines, chemokines, chemokine receptors, intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) also were observed. The stimulation of advanced glycation end products plus oxidized low-density lipoprotein, in cultured BMDCs, further activated toll-like receptor 4, protein kinase C and receptor of AGEs, and induced immune maturation of DCs through the RAGE-TLR4-PKCβ1 signaling pathway that was bound together by intrinsic structures on the cell membrane. Administering LY333531 significantly increased the body weight of diabetic ApoE−/− mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE−/− mice. Furthermore, the number of DCs and macrophages in atherosclerotic plaques was significantly reduced in the LY333531 group, and the collagen content was increased. Conclusions Diabetes mellitus aggravates chronic inflammation, and promotes atherosclerotic plaques in conjunction with hyperlipidemia, which at least in part through inducing the immune maturation of DCs, and its possible mechanism of action is through the RAGE-TLR4-pPKCβ1 signaling pathway. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1076-1551 1528-3658 |
| Relation: | https://doaj.org/toc/1076-1551; https://doaj.org/toc/1528-3658 |
| DOI: | 10.1186/s10020-022-00431-6 |
| URL الوصول: | https://doaj.org/article/08a052c846a8409e8570fdec485616cc |
| رقم الأكسشن: | edsdoj.08a052c846a8409e8570fdec485616cc |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 10761551 15283658 |
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| DOI: | 10.1186/s10020-022-00431-6 |