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LOX-1 参与了种植体周围炎中的 IL-1β 产生和细胞外基质降解。

LOX-1 is involved in IL-1β production and extracellular matrix breakdown in dental peri-implantitis.

机构信息

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

Department of Prosthodontics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

出版信息

Int Immunopharmacol. 2017 Nov;52:127-135. doi: 10.1016/j.intimp.2017.09.003. Epub 2017 Oct 12.

DOI:10.1016/j.intimp.2017.09.003
PMID:28898769
Abstract

PURPOSE

To explore whether lectin-type oxidized LDL receptor 1 (LOX-1), interleukin 1 beta (IL-1β), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) are involved in the nosogenesis of human dental peri-implantitis and determine the role of LOX-1 in IL-1β, MMP2 and MMP9 production in response to Porphyromonas gingivalis.

METHODS

Peri-implant crevicular fluid (PICF) was collected from ten patients with healthy implants and ten patients with peri-implantitis. The LOX-1 protein in PICF was detected by Western-blot, and the expression of LOX-1 in superficial gingiva of peri-implantitis patients was detected by immunofluorescence staining. The IL-1β, MMP2 and MMP9 proteins in PICF were detected by enzyme-linked immunosorbent assay (ELISA). THP-1 macrophages were pretreated with neutralizing antibody (LOX-1) and inhibitors (LOX-1 and c-Jun N-terminal kinase, JNK) to evaluate the role of LOX-1 and JNK in IL-1β production, as well as the role of LOX-1 in MMP2 and MMP9 production in response to P. gingivalis by quantitative polymerase chain reaction (RT-PCR) and Western-blot.

RESULTS

LOX-1, IL-1β, MMP2 and MMP9 increased in PICF of peri-implantitis patients and in THP-1 macrophages on P. gingivalis stimulation. IL-1β, MMP2 and MMP9 production in response to P. gingivalis in THP-1 macrophages was dependent on LOX-1. JNK was responsible for LOX-1 induced IL-1β production as a result of P. gingivalis infection.

CONCLUSION

LOX-1 is involved in IL-1β production and extracellular matrix breakdown is a novel inflammatory pathway trigger and potential drug target in human dental peri-implantitis.

摘要

目的

探讨凝集素型氧化型 LDL 受体 1(LOX-1)、白细胞介素 1β(IL-1β)、基质金属蛋白酶 2(MMP2)和基质金属蛋白酶 9(MMP9)是否参与人类牙周种植体周围炎的发病机制,并确定 LOX-1 在牙周种植体周围炎患者对牙龈卟啉单胞菌反应中产生 IL-1β、MMP2 和 MMP9 的作用。

方法

收集 10 例健康种植体患者和 10 例牙周炎患者的牙周袋液(PICF)。通过 Western-blot 检测 PICF 中的 LOX-1 蛋白,通过免疫荧光染色检测牙周炎患者牙龈表面的 LOX-1 表达。通过酶联免疫吸附试验(ELISA)检测 PICF 中的 IL-1β、MMP2 和 MMP9 蛋白。用中和抗体(LOX-1)和抑制剂(LOX-1 和 c-Jun N-末端激酶,JNK)预处理 THP-1 巨噬细胞,以评估 LOX-1 和 JNK 在 IL-1β产生中的作用,以及 LOX-1 在对牙龈卟啉单胞菌反应中产生 MMP2 和 MMP9 的作用,通过实时聚合酶链反应(RT-PCR)和 Western-blot 进行定量分析。

结果

牙周炎患者的 PICF 中 LOX-1、IL-1β、MMP2 和 MMP9 增加,THP-1 巨噬细胞在牙龈卟啉单胞菌刺激下也增加。THP-1 巨噬细胞对牙龈卟啉单胞菌的反应中,IL-1β、MMP2 和 MMP9 的产生依赖于 LOX-1。JNK 负责 LOX-1 诱导的牙龈卟啉单胞菌感染后产生的 IL-1β。

结论

LOX-1 参与了牙周炎患者的 IL-1β 产生,细胞外基质的破坏是人类牙周种植体周围炎的一种新的炎症途径触发因素和潜在的药物靶点。

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