Porphyromonas gingivalis infected macrophages upregulate CD36 expression via ERK/NF-κB pathway

Dong, Liang; Liu, Feng; Chen, Jianxia; He, Xiaoli; Zhou, Yunting; Ge, Baoxue; Luo, Lijun

doi:10.1016/j.cellsig.2016.05.017

Cited by 19 publications

(13 citation statements)

References 35 publications

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“…Similar results were reported for cells treated with soluble products of E. corrodens , which induced a pro‐inflammatory response as IL‐8 expression was induced by ERK1/2 . In macrophages, other periodontopathogens, such as P. gingivalis , also stimulate the nuclear translocation of p65 and the phosphorylation of ERK1/2, promoting the uptake of oxidized low‐density lipoprotein (ox‐LDL) and foam cell formation . We suggest that TLR‐4, ERK, and NF‐ k B p65 may play partial roles in the innate immunity of endothelial cells in response to E. corrodens ‐LPS.…”

Section: Discussionsupporting

confidence: 81%

“…The TLR‐4, NF κ B, and extracellular signal‐regulated kinase (ERK) pathways have recently been shown to be activated in HCAECs as a mechanism underlying the inflammatory response to stimuli characterized by cytokine and adhesion molecule production . Porphyromonas gingivalis and A. actinomycetemcomitans activate macrophages and HCAECs, respectively, through the ERK/NF‐ κ B signaling pathways . However, the mechanism by which E. corrodens and its endotoxins trigger pro‐inflammatory and pro‐atherosclerotic responses in HCAECs is completely unknown.…”

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confidence: 99%

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Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Viafara-García

Gualtero

Avila-Ceballos

et al. 2018

European J Oral Sciences

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Eikenella corrodens is a gram‐negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens‐LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM‐1) was determined using a cell‐based ELISA, and the adhesion of THP‐1 monocytes to HCAECs was also monitored. The involvement of toll‐like receptors (TLRs) 2 and 4 was examined using TLR‐neutralizing antibodies, and activation of extracellular signal‐regulated kinase (ERK)1/2 and nuclear factor‐kappa B (NF‐κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens‐LPS increased secretion of interleukin‐8 (IL‐8), monocyte chemotactic protein 1 (MCP‐1), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and expression of ICAM‐1 on the surface of HCAECs, consistent with the increased adhesion of THP‐1 cells. Moreover, E. corrodens‐LPS interacted with TLR4, a key receptor able to maintain the levels of IL‐8, MCP‐1, and GM‐CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF‐κB p65 were also increased. The results indicate that E. corrodens‐LPS activates HCAECs through TLR4, ERK, and NF‐κB p65, triggering a pro‐atherosclerotic endothelial response and enhancing monocyte adhesion.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Viafara-García

Gualtero

Avila-Ceballos

et al. 2018

European J Oral Sciences

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“…It might affect and accelerate the pathogenesis of AS through various machineries, such as increasing platelet aggregation, damaging vascular endothelial cells, promoting the formation of foam cells, and triggering the body's immune response 15 . Our previous study also confirmed that P. gingivalis encourages the expression of CD36 and increases the accumulation of lipids in cells through the ERK/NF‐κB signaling pathway, thereby promoting the formation of foam cells 16 . At the cellular level, the transformation from macrophages into foam cells induced by modified low‐density lipoprotein (LDL) is a hallmark of early AS 17 .…”

Section: Introductionsupporting

confidence: 53%

Porphyromonas gingivalis facilitated the foam cell formation via lysosomal integral membrane protein 2 (LIMP2)

Yang

Xia

et al. 2020

J of Periodontal Research

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Objective The involvement of lysosomal integral membrane protein 2 (LIMP2) in cholesterol transport and formation of foam cells under the infection of Porphyromonas gingivalis (P. gingivalis) is yet to be elucidated. The current study verified the role and explored the mechanism of LIMP2 in promoting foam cell formation by P. gingivalis. Background An association between periodontitis and atherosclerosis (AS) has been established. P. gingivalis is a key pathogen of periodontitis that promotes foam cell formation by regulating activities of CD36 scavenger receptors expressed on the macrophages. LIMP2, a member of CD36 superfamily, is involved in cholesterol efflux. However, whether LIMP2 is involved in the formation of foam cells promoted by P. gingivalis remains unclear. Methods The formation of foam cells was examined by Oil Red O staining. The knockdown of limp2 was identified by qRT‐PCR. The accumulation of cholesterol was monitored by Cholesterol Assay Kit. The location of P. gingivalis was visualized by confocal microscopy. Cathepsin L activity was monitored with Magic Red Cathepsin L Assay Kit. The key genes and pathways in P. gingivalis‐infected macrophages were explored by RNA sequencing. The protein level was investigated by Western blotting. Results Porphyromonas gingivalis increases foam cells formation and upregulates the expression of LIMP2 in foam cells. The knockdown of limp2 decreases the number of foam cells and increases cholesterol export, which is related to lysosomal functions. In addition, the interaction between LIMP2 and caveolin‐1(CAV1) might contribute to this process, and NF‐κB and JNK activity is required for increased expression of P. gingivalis‐induced LIMP2. Conclusions This study suggested that LIMP2 is involved in the foam cells formation facilitated by P. gingivalis, which favors a close connection between periodontitis and atherosclerosis (AS).

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“…In THP-1 cells, norepinephrine (NE) can induce the secretion of matrix metalloproteinase-9 (MMP-9) and augmented the progression of AS through promoting ERK/JNK-c-Fos pathway [ 45 ]. Plentiful evidence has also indicated that MAPKs and PI3K-Akt signal pathway can activate the downstream NF- κ B and enhance the progression of atherosclerosis [ 46 , 47 ]. Therefore, ERK-p38-NF- κ B and PI3K/Akt-NF- κ B signal transduction would be essential in the pathologic process of inflammatory disease such as AS.…”

Section: Discussionmentioning

confidence: 99%

Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3K/Akt Signal Pathway

Fei

Yuan

Zhao

et al. 2018

BioMed Research International

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Monocytes activation and subsequent inflammatory response mediated by monocyte-platelet aggregates (MPAs) formation play the key roles in the early pathogenesis of atherosclerosis (AS). Exploration of novel drugs to ameliorate MPAs formation-mediated monocytes activation would be helpful for the treatment of AS patients. Papain has definite pharmacological effects including antiplatelet, thrombolysis, and anti-inflammation. However, its effect on MPAs formation and the following monocytes activation remains vague. This study aimed to illustrate the underlying mechanisms of papain on MPAs formation-initiated monocytes activation in vitro. In this study, Papain, Cox-2 inhibitor (NS-398), and NF-κB agonist (TNF-α) were used as the treating agents, respectively. MPAs formation and activated monocytes were measured by flow cytometry (FCM). Cox-2 mRNA, MCP-1, and proteins of Cox-2 and NF-κB signal pathway were detected by qRT-PCR, ELISA, and western blotting, respectively. As we observed, papain exhibited the powerful inhibitory effects on thrombin-mediated MPAs formation and monocytes activation in a concentration-dependent manner as what Cox-2 inhibitor demonstrated. However, the inhibitory tendency was significantly reversed by TNF-α. We also discovered that both Cox-2 mRNA and protein expression as well as the release of MCP-1 of monocyte was inhibited by either papain or NS-398, but TNF-α stimulated Cox-2 expression and release of MCP-1. The results of western blotting assay indicated that thrombin-mediated proteins expression of MAPKs and PI3K/Akt signal pathway was inhibited by papain and NS-398. However, TNF-α notably abated the inhibitory effects of papain on the process of MPAs-initiated monocytes activation. Our findings suggest that papain can inhibit the MPAs formation-mediated activation of monocytes by inhibiting the MAPKs and PI3K/Akt signal pathway.

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Porphyromonas gingivalis infected macrophages upregulate CD36 expression via ERK/NF-κB pathway

Cited by 19 publications

References 35 publications

Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Eikenella corrodens lipopolysaccharide stimulates the pro‐atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Porphyromonas gingivalis facilitated the foam cell formation via lysosomal integral membrane protein 2 (LIMP2)

Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3K/Akt Signal Pathway

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