Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Shin, Soo Young; Kim, Young-Suk; Lee, So‐Youn; Bae, Won Kyung; Park, Yong-Duk; Hyun, Yong-Cheol; Kang, Kyung Lhi; Kim, Eun-Cheol

doi:10.1902/jop.2015.150123

Cited by 9 publications

(4 citation statements)

References 50 publications

(148 reference statements)

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“…Here, we demonstrate that HG exposure increases PLD1 and PLD2 mRNA levels in ARPE-19 cells. In agreement with our results, the inhibition or silencing of either PLD1 or PLD2 has been shown to inhibit nicotine- and LPS-induced ERK1/2 and NFκB activation, COX-2 expression, and secretion of tumor necrosis factor α, IL-1 β, and IL-8 in human periodontal ligament cells [ 36 ]. In addition, it has been reported that a high glucose environment induces and increases PLD1 expression in pancreatic beta cells [ 37 ].…”

Section: Discussionsupporting

confidence: 91%

Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels

Bermúdez

Tenconi

Echevarría

et al. 2022

IJMS

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We previously described the participation of canonical phospholipase D isoforms (PLD1 and PLD2) in the inflammatory response of retinal pigment epithelium (RPE) cells exposed to high glucose concentrations (HG). Here, we studied the role of the PLD pathway in RPE phagocytic function. For this purpose, ARPE-19 cells were exposed to HG (33 mM) or to normal glucose concentration (NG, 5.5 mM) and phagocytosis was measured using pHrodo™ green bioparticles® or photoreceptor outer segments (POS). HG exposure for 48 and 72 h reduced phagocytic function of ARPE-19 cells, and this loss of function was prevented when cells were treated with 5 μM of PLD1 (VU0359595 or PLD1i) or PLD2 (VU0285655-1 or PLD2i) selective inhibitors. Furthermore, PLD1i and PLD2i did not affect RPE phagocytosis under physiological conditions and prevented oxidative stress induced by HG. In addition, we demonstrated PLD1 and PLD2 expression in ABC cells, a novel human RPE cell line. Under physiological conditions, PLD1i and PLD2i did not affect ABC cell viability, and partial silencing of both PLDs did not affect ABC cell POS phagocytosis. In conclusion, PLD1i and PLD2i prevent the loss of phagocytic function of RPE cells exposed to HG without affecting RPE function or viability under non-inflammatory conditions.

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Section: Discussionsupporting

confidence: 91%

Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels

Bermúdez

Tenconi

Echevarría

et al. 2022

IJMS

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“…Here resistin showed the regulation of these factors and exerted antiinflammatory effects on this chronic periodontal disease cell model (78). Nicotine plus LPS likewise upregulated iNOS, COX-2, NO, PGE2, TNF-a, IL-1b, IL-8, some TRAP (+) cells, and resorption via PI3K/PKC/Akt/MAPK (P38, JNK, ERK) and the NF-kB/c-Fos/NFATc1 signaling axis, involved in inflammatory bone destruction and osteoclast differentiation, with an increase in phospholipase D (PLD) 1 and PLD2 isoforms (79). When human periodontal ligament cells were cocultured with CD4 + T cells, nicotine (10 -5 M, 24 h) dramatically repressed cell viability and increased apoptosis, which was associated with the collapse of periodontal tissues and elevated matrix metalloproteinases MMP1, MMP3, and cytokines IL-1b, IL-6, IL-17, IL-21, and chemokines CXCL12.…”

Section: Pro-inflammatory Effect Of Nicotine On Oral Diseasesmentioning

confidence: 99%

Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects

et al. 2022

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As an anti-inflammatory alkaloid, nicotine plays dual roles in treating diseases. Here we reviewed the anti-inflammatory and pro-inflammatory effects of nicotine on inflammatory diseases, including inflammatory bowel disease, arthritis, multiple sclerosis, sepsis, endotoxemia, myocarditis, oral/skin/muscle inflammation, etc., mainly concerning the administration methods, different models, therapeutic concentration and duration, and relevant organs and tissues. According to the data analysis from recent studies in the past 20 years, nicotine exerts much more anti-inflammatory effects than pro-inflammatory ones, especially in ulcerative colitis, arthritis, sepsis, and endotoxemia. On the other hand, in oral inflammation, nicotine promotes and aggravates some diseases such as periodontitis and gingivitis, especially when there are harmful microorganisms in the oral cavity. We also carefully analyzed the nicotine dosage to determine its safe and effective range. Furthermore, we summarized the molecular mechanism of nicotine in these inflammatory diseases through regulating immune cells, immune factors, and the vagus and acetylcholinergic anti-inflammatory pathways. By balancing the “beneficial” and “harmful” effects of nicotine, it is meaningful to explore the effective medical value of nicotine and open up new horizons for remedying acute and chronic inflammation in humans.

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“…Periodontal disease is characterized by an inflammatory reaction of periodontal tissue that leads to the progressive destruction of tooth-associated structures including alveolar bone, periodontal ligament (PDL) and cementum [ 2 ]. PDL cells (PDLCs) located between the tooth cementum and bone play a major role in alveolar bone metabolism in periodontal health and disease because of their ability to secrete factors that regulate the homeostasis of connective and osseous tissue, including inflammatory cytokines and major osteoblast or osteoclast regulators [ 3 , 4 , 5 , 6 ]. Cementoblasts are responsible for the production of cementum, which is the gold standard in periodontal regeneration [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

Bae

Park

Kang

et al. 2018

IJMS

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The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (SASP) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.

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Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Abstract: To the best of the authors' knowledge, this study is the first to demonstrate that PLD isoform inhibition has anti-inflammatory and antiosteoclastogenic effects and thus may be a therapeutic target for the treatment of periodontitis.

Cited by 9 publications

References 50 publications

Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels

Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels

Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

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