Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model

Sheng, Qingfeng; Lv, Zhibao; Cai, Wei; Song, Huan-Lei; Qian, Liying; Mu, Huaibo; Shi, Jingyi; Wang, Xueli

doi:10.1038/pr.2014.93

Cited by 39 publications

(46 citation statements)

References 36 publications

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“…It can be either proinflammatory or anti-inflammatory, depending on the circumstances [38, 39]. In addition, the beneficial effects of hBD3 on wound healing were also reported [40]. We previously demonstrated that hBD3 significantly inhibited the progression of early-stage atherosclerotic lesions, and this effect was correlated with downregulation of macrophage inflammation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…But the main objective of the present study was to evaluate the anti-inflammatory effect of hBD3, which might provide a novel therapeutic strategy for clinical application. And the use of recombinant proteins of human origin is widely used in animal studies; for example, application of hBD3 in both mice and rats have been reported [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…However, hBD3 was shown to display anti-inflammatory properties by reducing the expression of pro-inflammatory cytokines in necrotizing enterocolitis in a neonatal rat model [33]. Additionally, hBD3 has been reported to inhibit the E. coli LPS-induced production of TNF-α by RAW 264.7 cells and bone marrow-derived macrophages and to prevent endotoxin shock in mice [32].…”

Section: Introductionmentioning

confidence: 99%

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

Bian

Lyu

et al. 2016

Peptides

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“…2e), but was not indicative of disease severity (Refs 88, 93, 94, 95). Ileal and systemic TNF were also increased in rat models of NEC (Refs 96, 97, 98), with the mRNA rising as early as 1.5 h after the first feed (Ref. 99).…”

Section: Mediators Of Innate Immunitymentioning

confidence: 99%

The immunological landscape in necrotising enterocolitis

Cho

Berger

Nold-Petry

et al. 2016

Expert Rev. Mol. Med.

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Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.

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Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model

Cited by 39 publications

References 36 publications

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

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

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

The immunological landscape in necrotising enterocolitis

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