胃泌素释放肽受体拮抗剂 RC-3095 通过抑制内皮细胞和巨噬细胞的炎症反应,抑制牙龈卟啉菌脂多糖加速动脉粥样硬化。

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2024-11-01 Epub Date: 2024-08-20 DOI:10.1007/s00011-024-01934-0
Hyun-Joo Park, Mi-Kyoung Kim, Yeon Kim, Hyung Joon Kim, Hae Ryoun Park, Soo-Kyung Bae, Moon-Kyoung Bae
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引用次数: 0

摘要

目的:牙龈卟啉单胞菌(P:牙龈卟啉单胞菌(P. gingivalis)是主要的牙周致病菌之一,与动脉粥样硬化的进展和恶化有关。在这项研究中,我们旨在探讨胃泌素释放肽受体拮抗剂 RC-3095 能否减轻牙龈弧菌 LPS 诱导的内皮细胞和巨噬细胞炎症反应,以及载脂蛋白E-/-小鼠模型中的动脉粥样硬化:方法:使用 HUVECs 和大鼠主动脉内皮细胞研究 RC-3095 对牙龈脓毒性 LPS 诱导的内皮炎症的影响。将 THP-1 细胞暴露于 P. gingivalis LPS,加入或不加入 RC-3095 将其极化为 M1 巨噬细胞。通过注射 P. gingivalis LPS、RC-3095 或两者的组合,评估 RC-3095 对高脂雄性载脂蛋白 E-/- 小鼠动脉粥样硬化进展的影响:结果:RC-3095 通过抑制 ICAM-1 和 VCAM-1 的 NF-κB 依赖性表达,明显降低了牙龈脓肿 LPS 诱导的白细胞对内皮细胞和主动脉内皮的粘附。此外,RC-3095 还能通过阻断 MAPK 和 NF-κB 信号通路,抑制牙龈脓肿 LPS 诱导的 M1 巨噬细胞极化。此外,RC-3095 还能减少 ApoE-/- 小鼠动脉粥样硬化病变的面积,而 P. gingivalis LPS 注射会加速动脉粥样硬化病变的面积,并降低动脉粥样硬化小鼠主动脉组织中 ICAM-1 和 VCAM-1 的表达:结论:RC-3095能缓解牙龈脓毒性球菌LPS诱导的内皮炎症、巨噬细胞极化和动脉粥样硬化进展,表明它有可能成为牙周病原体相关动脉粥样硬化的一种治疗方法。
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Gastrin-releasing peptide receptor antagonist RC-3095 inhibits Porphyromonas gingivalis lipopolysaccharide-accelerated atherosclerosis by suppressing inflammatory responses in endothelial cells and macrophages.

Objective: Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE-/- mouse model treated with P. gingivalis LPS.

Methods: The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE-/- mice through injections of P. gingivalis LPS, RC-3095, or a combination of both.

Results: RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE-/- mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis.

Conclusions: RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis.

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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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