Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by <scp>LPS</scp> in human dental pulp cells

Jung, Ji‐Yeon; Woo, Su-Mi; Kim, W. J.; Lee, B. N.; Min, Kyung-San; Choi, Chul-Hee; Koh, Joon; Lee, K. J.; Hwang, Yun Chan

doi:10.1111/iej.12635

Cited by 41 publications

(34 citation statements)

References 38 publications

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“…Oral inflammatory diseases are mainly caused by bacteria infections to the dentin or root canal . LPS, the main bacteria toxoid, induces inflammatory cytokines IL‐1, ‐6, ‐8 and TNF‐α and inflammatory molecules, matrix metalloproteinases (MMP‐9 and MMP‐2) in human peripheral blood mononuclear cells, dental pulp cells and gingival fibroblasts . In this study, a low concentration of phelligridin D , eg, <5 μmol/L, did not have cytotoxicity in HDPLCs.…”

Section: Discussionmentioning

confidence: 59%

Anti‐inflammatory character of Phelligridin D modulates periodontal regeneration in lipopolysaccharide‐induced human periodontal ligament cells

Kim

Takanche

Yun

et al. 2018

J of Periodontal Research

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Section: Discussionmentioning

confidence: 59%

Anti‐inflammatory character of Phelligridin D modulates periodontal regeneration in lipopolysaccharide‐induced human periodontal ligament cells

Kim

Takanche

Yun

et al. 2018

J of Periodontal Research

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“…NF-?B has an important role in the inflammatory response, and NF-?B activation was shown to regulate the IL-8 level [45]. Several studies have reported that LPS modulates the expression of cytokines and adhesion molecules, and these alterations play a crucial role in the pathogenesis of systemic inflammatory reactions [46]. LPS-treated HUVECs release ROS, and a mechanism that involves ROS and NF-?B activation could at least partially explain the cytokine induction in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial Dysfunction and Activation of Nrf2

Zhang¹,

Pan²,

Xu³

et al. 2017

Cell Physiol Biochem

106

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Background: Allicin, a major component of garlic, is regarded as a cardioprotective agent and is associated with increased endothelial function. Methods: The effects of allicin on lipopolysaccharide (LPS)-induced vascular oxidative stress and inflammation in cultured human umbilical vein endothelial cells (HUVECs) and the mechanisms underlying these effects were studied. The protective effects were measured using cell viability, a lactate dehydrogenase (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was determined by measuring reactive oxygen species (ROS) generation, oxidative products and endogenous antioxidant enzyme activities. HUVEC mitochondrial function was assessed by determining mitochondrial membrane potential (MMP) collapse, cytochrome c production and mitochondrial ATP release. To investigate the potential underlying mechanisms, we also measured the expression of dynamic mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2 antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA). Results: Our results demonstrated that allicin enhanced HUVEC proliferation, which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS-induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and decreased the endogenous antioxidant enzyme activities in HUVECs. These protective effects were associated with the inhibition of mitochondrial dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced inflammatory responses, including endothelial cell adhesion and TNF-α and IL-8 production. Furthermore, allicin increased the expression of LXRα in a dose-dependent manner. Allicin-induced attenuation of inflammation was inhibited by LXRα siRNA treatment. Finally, allicin activated NF-E2-related factor 2 (Nrf2), which controls the defense against oxidative stress and inflammation. Conclusions: Taken together, the present data suggest that allicin attenuated the LPS-induced vascular injury process, which may be closely related to the oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2 activation and protected the cells against LPS-induced vascular injury. Our findings suggest that allicin attenuated the LPS-induced inflammatory response in blood vessels.

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“…In addition to macrophages, LPS induces inflammatory cytokine expression in human dental pulp cells (hDPCs) (Jung et al . , Widbiller et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…Pulp tissue lacks collateral circulation and exists in a low compliance environment, which induces high internal pressure if inflammation is evoked. In addition to macrophages, LPS induces inflammatory cytokine expression in human dental pulp cells (hDPCs) (Jung et al 2017, Widbiller et al 2018. A greater proportion of Gram-negative bacteria have been reported to be present in the cariogenic microflora of deep cavities (Aas et al 2008), and the application of LPS to dentinal surfaces without pulp exposure was sufficient to induce pulpal inflammation in mouse molars (Chung et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Heparin–LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS‐neutralizing abilities

Yoshida

Suzuki²,

Kawada‐Matsuo

et al. 2019

Int Endodontic J

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Aim To investigate whether glycosaminoglycans (GAGs) binding to high‐dose LL37 eliminates its cytotoxicity to dental pulp cells (hDPCs) whilst retaining undiminished antimicrobial and LPS‐neutralizing abilities. Methodology hDPCs were stimulated with varying concentrations of LL37, and their cell viability was analysed by MTT. Then, high‐dose LL37 (10 μmol L−1) was bound to varying concentrations of three GAGs, heparin, chondroitin sulphate and hyaluronic acid, and their cytotoxic effects on hDPCs and antimicrobial effects were evaluated and compared. Furthermore, the LPS‐neutralizing ability of heparin (5 μg mL−1)–LL37 (10 μmol L−1) complexes, which were found to be less cytotoxic for hDPCs with undiminished antimicrobial ability, was investigated. Statistical analysis was performed using one‐way analysis of variance (anova), followed by Dunnett's test. P values below 0.05 were considered significant. Results LL37 significantly reduced the cell viability of hDPCs in a dose‐dependent manner (P < 0.01). LL37 (10 μmol L−1) binding to heparin within a limited concentration range (2~6 μg mL−1) eliminated the cytotoxicity for hDPCs (P < 0.01) whilst exerting potent antimicrobial effects against Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Aggegatibacter actinomycetemcomitans and Escherichia coli. LL37 (10 μmol L−1) binding to chondroitin sulphate exhibited similar functions (P < 0.01); however, the effective chondroitin sulphate concentration was highly restricted (3 μg mL−1). LL37 (10 μmol L−1) binding to hyaluronic acid was unable to abrogate the cytotoxicity of LL37 even at higher concentrations (10 and 100 μg mL−1). Moreover, exogenous addition of LPS dose‐dependently reduced the amount of LL37 precipitated with the heparin–LL37 agarose beads (P < 0.01), and the released LL37 simultaneously neutralized the pro‐inflammatory ability of LPS in macrophages (P < 0.01). Conclusions Heparin–LL37 complexes generated at suitable concentration ratios are easy to make, are less cytotoxic and are broad‐range antimicrobial materials that can neutralize LPS by providing LL37 in accordance with the amount of free LPS. They may be a potential treatment to save dental pulp tissue from the acute inflammation exacerbated by invading bacteria and the LPS they release.

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Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells

Abstract: Simvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy.

Cited by 41 publications

References 38 publications

Anti‐inflammatory character of Phelligridin D modulates periodontal regeneration in lipopolysaccharide‐induced human periodontal ligament cells

Anti‐inflammatory character of Phelligridin D modulates periodontal regeneration in lipopolysaccharide‐induced human periodontal ligament cells

Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial Dysfunction and Activation of Nrf2

Heparin–LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS‐neutralizing abilities

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