STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: A plausible regional mechanism of immunosuppression in arsenical cancers

Hong, Chien Hui; Lee, Chih Hung; Chen, Gwo Shing; Chang, Kee-Lung; Yu, Hsin Su

doi:10.1016/j.cbi.2014.12.030

Cited by 16 publications

(14 citation statements)

References 50 publications

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“…As-induced activation of NF-κB, a transcription factor involved in CRP expression [41], was prevented by pretreatment with NAC in cultured aortic endothelial cells, suggesting that oxidation of thiols was responsible for the activation of NF-κB [19]. Other transcription factors involved in CRP expression, including C/EBPβ and STAT3 [40], may also be activated by As [50,51]. Because the redox environment can modulate activation of NF-κB [52], STAT3 [53,54], and possibly C/EBPβ [55], it is possible that in a low GSH/more oxidized redox environment, As-induced redox changes mediate the effect of As on CRP, in accordance with our results.…”

Section: Discussionmentioning

confidence: 99%

Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

Peters

Liu

Hall

et al. 2015

Free Radical Biology and Medicine

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Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (EhGSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs pWald = 0.03; bAs pWald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by EhGSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma EhGSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma EhGSH and reduces risk for As-induced diseases.

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Section: Discussionmentioning

confidence: 99%

Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

Peters

Liu

Hall

et al. 2015

Free Radical Biology and Medicine

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“…Transendothelial migration was determined using a Transwell system and the results showed that transmigration capability of mDCs was markedly diminished after treatment with 50 ng/mL VEGF (Figure 3). Previous studies have also suggested that the TME and TGF-β 1 cytokine can lead to improper migration of DCs [20,21,29,34]. That also further confirmed that the decreased EPM, hypo-osmolality resistance, and deformability of DCs can adversely affect their motility and may be one of the explanations for why only a few tumor-stimulated DCs can migrate to the lymph nodes after intracutaneous injection [41].…”

Section: Resultsmentioning

confidence: 55%

“…It can promote tumor angiogenesis and inhibit DCs’ differentiation and functional maturation [32,33,34,35,36]. At present, some signaling pathways, such as fms-related tyrosine kinase 1 (Flt-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription 3 (STAT3), have been proven to be involved with the suppression of DCs’ function [34,37,38]. However, it is unclear whether the dysfunction of DCs by VEGF is related to the impairment of biophysical properties and motility.…”

Section: Introductionmentioning

confidence: 99%

Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling

Xue

Long

et al. 2016

IJMS

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Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors.

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“…Interestingly, As did not affect MHC-II surface levels, which might explain the reduced T-cell proliferation-inducing capacity of As-treated MoDC (Mehrzad et al 2015). Immunotoxicologically though incomparable, nonetheless, this diminished T-cell proliferationinducing activity is in line with a diminished cell-mediated immunity in piglets fed with other environmental toxicants (Meissonnier et al 2008;Hong et al 2015). Other DC surface molecules/markers (e.g.…”

Section: Discussionmentioning

confidence: 93%

“…Changes in these parameters are often used to assess the immunotoxic effects of environmental toxins, such as mycotoxins (Devriendt et al 2009;Hong et al 2015). Exposure to As affected the cell surface marker expression by porcine DC.…”

Section: Discussionmentioning

confidence: 99%

Effects of arsenic on porcine dendritic cells in vitro

Mehrzad

Gharaie

Taheri

2017

Journal of Immunotoxicology

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Exposure to arsenic (As) is an ongoing, and in some places increasing, health problem. Still, however, the effects of As exposure on the immune system are not well understood. Dendritic cells (DC) are a critical immune cell that bridges the innate and adaptive immune systems. To determine the impact of inorganic (i)As exposure on DC, the effects of (geo)anthropogenically relevant levels of NaAsO 2 on the function of porcine monocyte-derived DC (MoDC) were evaluated in an in vitro model. The results showed a low dose of iAs reduced the phagocytic capacity of MoDC. Furthermore, although surface expression of DC activation markers, such as major histocompatibility complex (MHC)-II, CD80/86, CD40 and CD25, were only slightly changed, MoDC T-cell proliferation-inducing capacity was remarkably diminished by iAs treatment. Additionally, iAs induced significant interleukin (IL)-6 secretion by MoDC after 12-or 24-h incubation, whereas IL-1b secretion was only significantly up-regulated after 12 h. The secretion patterns of IL-8, tumor necrosis factor a (TNFa and IL-10 by iAs-treated MoDC were almost similar to that by mock-treated MoDC. Considering the broad roles of DC in immunobiology, this finding deepens the understanding of molecular mechanisms/functional consequences underpinning the immunopathology, inflammation, and increases in infection arising from As exposure. ARTICLE HISTORY

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STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: A plausible regional mechanism of immunosuppression in arsenical cancers

Cited by 16 publications

References 50 publications

Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling

Effects of arsenic on porcine dendritic cells in vitro

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