Human β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice

Bian, Tianying; Li, Lili; Lyu, Jinglu; Cui, Di; Lei, Lang; Yan, Fuhua

doi:10.1016/j.peptides.2016.06.002

Cited by 19 publications

(15 citation statements)

References 37 publications

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“…Previous studies revealed that BD3 reduces the phosphorylation of p38 and c-Jun MAPK pathway in human umbilical vein endothelial cells ( 45 ). Bian and colleagues have recently found that BD3 is involved in the attenuation of the phosphorylation of p38 and ERK1/2 in MAPK pathway ( 13 ). Thus, we speculated that MAPK signaling may contribute in the BD2 and BD3-mediated suppression of EGR1 and c-FOS in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…It is also reported that BDs are capable of electrostatically interacting with negatively charged components in microbial cell walls, by increasing the permeability of cell walls and ultimately leading to a host cell death ( 9 ). In addition to their antimicrobial function, BDs also function as inflammatory mediators, with impact on the immune activation of epithelial cells and immunocytes ( 10 , 11 ), production of inflammatory cytokines ( 12 , 13 ), as well as induction of chemotaxis ( 7 , 14 ). For instance, Beta-defensins 2 (BD2) has been shown to chemoattract immature dendritic cells or memory CD4 + T cells through C–C motif chemokine receptor 6 ( 7 ), while beta-defensins 3 (BD3) and BD4 recruit macrophages dependent on cysteine residues ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Wang

et al. 2018

Front. Immunol.

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Beta-defensins 2 and 3 (BD2 and BD3) are inducible peptides present at the sites of infection, and they are well characterized for their antimicrobial activities and immune-regulatory functions. However, no study has thoroughly investigated their immunomodulatory effects on macrophage-mediated immune responses against Pseudomonas aeruginosa (PA). Here, we use THP-1 and RAW264.7 cell lines and demonstrate that BD2 and BD3 suppressed macrophage autophagy but enhanced the engulfment of PA and Zymosan bioparticles as well as the formation of phagolysosomes, using immunofluorescence staining and confocal microscopy. Plate count assay showed that macrophage-mediated phagocytosis and intracellular killing of PA were promoted by BD2 and BD3. Furthermore, microarray and real-time PCR showed that the expression of two genes, early growth response gene-1 (EGR1) and c-FOS, was attenuated by BD2 and BD3. Western blot revealed that BD2 and BD3 inhibited the expression and nuclear translocation of EGR1 and c-FOS. Knockdown of EGR1 and c-FOS by siRNA transfection suppressed macrophage autophagy before and after PA infection; while overexpression of these two transcription factors enhanced autophagy but reversed the role of BD2 and BD3 on macrophage-mediated PA eradication. Together, these results demonstrate a novel immune defense activity of BD2 and BD3, which promotes clearance of PA by inhibiting macrophage autophagy through downregulation of EGR1 and c-FOS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Wang

et al. 2018

Front. Immunol.

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“…In our previous study, the results demonstrated that chronic exposure to the endotoxin of Porphyromonas gingivalis can aggravate atherosclerotic lesions in ApoE-deficient mice [6]. Indeed, compelling evidence has demonstrated the proatherogenic role of inflammatory cytokines in the pathogenesis of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Humanβ-Defensin 3 Reduces TNF-α-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells

Bian

Zhou

et al. 2017

Mediators of Inflammation

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The aim of this study was to investigate the role of human β-defensin 3 (hBD3) in the initiation stage of atherosclerosis with human umbilical vein endothelial cells (HUVECs) triggered by tumor necrosis factor- (TNF-) α. The effects of hBD3 on TNF-α-induced endothelial injury and inflammatory response were evaluated. Our data revealed that first, hBD3 reduced the production of interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF) in HUVECs in a dose-dependent manner. In addition, hBD3 significantly prevented intracellular reactive oxygen species (ROS) production by HUVECs. Second, western blot analysis demonstrated that hBD3 dose-dependently suppressed the protein levels of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-induced HUVECs. As a result, hBD3 inhibited monocyte adhesion to TNF-α-treated endothelial cells. Additionally, hBD3 suppressed TNF-α-induced F-actin reorganization in HUVECs. Third, hBD3 markedly inhibited NF-κB activation by decreasing the phosphorylation of IKK-α/β, IκB, and p65 subunit within 30 min. Moreover, the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway were also inhibited by hBD3 in HUVECs. In conclusion, hBD3 exerts anti-inflammatory and antioxidative effects in endothelial cells in response to TNF-α by inhibiting NF-κB and MAPK signaling.

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“…The hBD3 possess a broad spectrum of antimicrobial activity against many pathogenic microbes, including Grampositive and Gram-negative bacteria, fungi (Batoni et al, 2006), and different viruses such as HIV, IAV, VSV, HBV, HPV, HSV, CVB3 and vaccinia virus (Ding et al, 2009;Hazrati et al, 2006;Jiang et al, 2015;Wilson et al, 2013). It is involved in different infectious diseases progress and immune regulations (Bian et al, 2016;Li et al, 2016;Szekeres et al, 2016;Wanke et al, 2016;Xu et al, 2016). It has been reported that hBD3 can block IAV, HSV, and HIV entry into cells by cross linking and immobilizing viral surface proteins (Hazrati et al, 2006;Leikina et al, 2005;Quinones-Mateu et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Induction and antiviral activity of human β-defensin 3 in intestinal cells with picornavirus infection

W¹,

Z²,

Zhang³

et al. 2018

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Antimicrobial peptides produced by epithelial and immune cells protect tissues from various infections. Whether enterovirus infection leads to stimulation of antimicrobial peptide expression is unknown. We examined antimicrobial peptide mRNA and protein production in HT-29 colon adenocarcinoma cells infected with picornaviruses. The antiviral activity of increased antimicrobial peptide production was evaluated by using a recombinant peptide and corresponding gene overexpression. Enterovirus infection enhanced both the mRNA expression and secretion of human β-defensin (hBD) 3 in intestinal epithelial cells but did not increase expression of human neutrophil peptide 1-3 (HNP 1-3), HNP4, human defensin 5 (HD5), HD6, hBD1, hBD2, and hBD5. The recombinant but not the intracellularly overexpressed hBD3 inhibited enterovirus (EV) 71, coxsackievirus A16 (CVA16), CVB5 and poliovirus 1 (PV1) infecting HT-29 cells. Our results suggest that enterovirus infection induces hBD3 production in human intestinal epithelial cells and that hBD3 can exert extracellular anti-enterovirus activity.

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Human β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice

Cited by 19 publications

References 37 publications

Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Humanβ-Defensin 3 Reduces TNF-α-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells

Induction and antiviral activity of human β-defensin 3 in intestinal cells with picornavirus infection

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