Porphyromonas gingivalis lipopolysaccharide induced RIPK3/MLKL-mediated necroptosis of oral epithelial cells and the further regulation in macrophage activation.
Porphyromonas gingivalis lipopolysaccharide induced RIPK3/MLKL-mediated necroptosis of oral epithelial cells and the further regulation in macrophage activation.
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牙龈卟啉单胞菌脂多糖诱导RIPK3/MLKL介导的口腔上皮细胞坏死性凋亡及其对巨噬细胞活化的进一步调控
DOI：
10.1080/20002297.2022.2041790
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发表时间：
2022
影响因子：
4.5
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Geng F;Liu J;Yin C;Zhang S;Pan Y;Sun H
摘要坏死性凋亡是一种新型的调节性细胞死亡，伴随着损伤相关分子模式（DAMPs）的大量释放，参与牙周炎的发病。然而，口腔上皮细胞中坏死性凋亡的作用以及对巨噬细胞活化的影响仍然未知。用牙龈卟啉单胞菌脂多糖（LPS）刺激人永生化口腔上皮细胞。评估细胞死亡，同时评价RIPK 3/MLKL和toll样受体（TLR）的表达。应用MLKL抑制剂Necrosulfonamide（NSA）阻断坏死性凋亡。分别通过qPCR和免疫荧光评价DAMPs和上皮连接蛋白的表达。将永生化的人单核细胞U937诱导为M0或M2亚群，并评估HIOEC衍生的DAMP对巨噬细胞极化以及Mincle/SYK轴活化的影响。牙龈卟啉单胞菌LPS可被TLR 2识别，并通过激活RIPK 3/MLKL调节HIOEC的坏死性凋亡。NSA抑制HIOEC的细胞死亡，减轻受损的上皮连接，并抑制DAMPs的表达。低剂量的DAMPs通过激活Mincle/SYK轴来促进M2样极化，这随着DAMPs剂量的增加而被显著抑制。牙龈卟啉单胞菌LPS通过RIPK 3/MLKL介导的坏死性凋亡破坏口腔上皮细胞，其通过来自口腔上皮细胞的DAMP进一步调节巨噬细胞活化。
ABSTRACT Necroptosis, a new type of regulated cell death with massive release of damage-associated molecular patterns (DAMPs), is involved in the pathogenesis of periodontitis. However, the role of necroptosis in oral epithelial cells and the following effect on macrophages activation remain unknown. Human immortalized oral epithelial cells were stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Cell death was assessed while expressions of RIPK3/MLKL and toll-like receptors (TLRs) were evaluated. Necrosulfonamide (NSA), an inhibitor of MLKL was applied to block necroptosis. The expression of DAMPs and the epithelial connection protein were evaluated by qPCR and immunofluorescence, respectively. Immortalized human monocytes U937 were induced into the M0 or M2 subset, and influences of HIOECs-derived DAMPs on macrophage polarization as well as activation of the Mincle/SYK axis were assessed. P. gingivalis LPS could be recognized by TLR2 and regulates necroptosis of HIOECs by activating RIPK3/MLKL. NSA inhibited cell death of HIOECs, alleviated impaired epithelial connection, and inhibited expressions of DAMPs. Low dose of DAMPs derived from HIOECs promoted M2-like polarization by activating the Mincle/SYK axis, which was significantly suppressed with increased doses of DAMPs. P. gingivalis LPS destructed oral epithelial cells via RIPK3/MLKL-mediated necroptosis, which further regulated macrophage activation via DAMPs from oral epithelial cells.
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影响因子：
32.4
作者：
Iborra, Salvador;Martinez-Lopez, Maria;Cueto, Francisco J.;Conde-Garrosa, Ruth;Del Fresno, Carlos;Izquierdo, Helena M.;Abram, Clare L.;Mori, Daiki;Campos-Martin, Yolanda;Maria Reguera, Rosa;Kemp, Benjamin;Yamasaki, Sho;Robinson, Matthew J.;Soto, Manuel;Lowell, Clifford A.;Sancho, David
通讯作者：
Sancho, David
模式识别受体 Mincle 对于维持急性肾脏炎症中的 M1 巨噬细胞表型至关重要
影响因子：
19.6
作者：
Lv, Lin L.;Tang, Patrick Ming-Kuen;Lan, Hui-Yao
通讯作者：
Lan, Hui-Yao
影响因子：
4.6
作者：
Li, Jiao;Shi, Jiahong;Lei, Lang
通讯作者：
Lei, Lang
抑制 RIPK1/RIPK3/MLKL 介导的角质细胞坏死性凋亡可提供针对银屑病炎症的保护作用
影响因子：
9
作者：
Duan, Xiaoru;Liu, Xinxin;Chen, Hongxiang
通讯作者：
Chen, Hongxiang
影响因子：
7.6
作者：
Chen, W.;Alshaikh, A.;Kang, M. K.
通讯作者：
Kang, M. K.