PM2.5 Induced the Expression of Fibrogenic Mediators via HMGB1-RAGE Signaling in Human Airway Epithelial Cells

Zou, Weifeng; He, Fang; Li, Sha; Pu, Jinding; Hu, Jinxing; Sheng, Qing; Tao, Zhu; Zhu, Tianhua; Li, Bing; Ran, Pixin

doi:10.1155/2018/1817398

Cited by 18 publications

(12 citation statements)

References 22 publications

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“…These data in corneal epithelial cells are consistent with a study in mouse lung (alveolar) macrophages, providing evidence that PM 2.5 induced increases in mRNA levels of molecules also associated with innate immunity, such as TLR4, IL-1β and TNF-α. 60 The data also are consistent with studies using human airway epithelial cells, which showed that HMGB1 mRNA levels were elevated 61 and other work that provided evidence that SOD and GPX1 levels in plasma 62 were significantly increased after particulate exposure.…”

Section: Discussionsupporting

confidence: 88%

Airborne Particulates Affect Corneal Homeostasis and Immunity

Somayajulu

Ekanayaka

McClellan

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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To determine the effects of airborne particulate matter (PM) <2.5 μm in vitro and on the normal and Pseudomonas aeruginosa (PA)-infected cornea. METHODS. An MTT viability assay tested the effects of PM 2.5 on mouse corneal epithelial cells (MCEC) and human corneal epithelial cells (HCET). MCEC were tested for reactive oxygen species using a 2 ,7-dichlorodihydrofluorescein assay; RT-PCR determined mRNA levels of inflammatory and oxidative stress markers in MCEC (HMGB1, toll-like receptor 2, IL-1β, CXCL2, GPX1, GPX2, GR1, superoxide dismutase 2, and heme oxygenase 1) and HCET (high mobility group box 1, CXCL2, and IL-1β). C57BL/6 mice also were infected and after 6 hours, the PM 2.5 was topically applied. Disease was graded by clinical score and evaluated by histology, plate count, myeloperoxidase assay, RT-PCR, ELISA, and Western blot. RESULTS. After PM 2.5 (25-200 μg/mL), 80% to 90% of MCEC and HCET were viable and PM exposure increased reactive oxygen species in MCEC and mRNA expression levels for inflammatory and oxidative stress markers in mouse and human cells. In vivo, the cornea of PA+PM 2.5 exposed mice exhibited earlier perforation over PA alone (confirmed histologically). In cornea, plate counts were increased after PA+PM 2.5 , whereas myeloperoxidase activity was significantly increased after PA+PM 2.5 over other groups. The mRNA levels for several proinflammatory and oxidative stress markers were increased in the cornea in the PA+PM 2.5 over other groups; protein levels were elevated for high mobility group box 1, but not toll-like receptor 4 or glutathione reductase 1. Uninfected corneas treated with PM 2.5 did not differ from normal. CONCLUSIONS. PM 2.5 triggers reactive oxygen species, upregulates mRNA levels of oxidative stress, inflammatory markers, and high mobility group box 1 protein, contributing to perforation in PA-infected corneas.

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Section: Discussionsupporting

confidence: 88%

Airborne Particulates Affect Corneal Homeostasis and Immunity

Somayajulu

Ekanayaka

McClellan

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…The details of PM2.5 samples and analysis methods can be found in our previous research. 12 The PM2.5 sample was stored at −80°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction and Western blot were performed according to our previous description 12 and the manufacturer’s instructions. The concentrations of the antibodies were as follows: Wnt5a antibody (1:1000), Ror2 antibody (1:1000), and NF-κB p65 antibody (1:1000, Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

<p>PM2.5 Induces the Expression of Inflammatory Cytokines via the Wnt5a/Ror2 Pathway in Human Bronchial Epithelial Cells</p>

Zou

Wang

et al. 2020

COPD

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Background and Purpose Recently, fine particulate matter (PM2.5) was identified as the main exposure risk for COPD, and inflammation is central to the development of COPD. In this study, we investigated whether PM2.5 can induce the secretion of interleukin-6 (IL-6), IL-8 and IL-1β in human bronchial epithelial cells (HBECs) in vitro via the wingless-related integration site 5A (Wnt5a)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling. Methods The expression of Wnt5a and Ror2 was assessed by immunohistochemistry in motor vehicle exhaust (MVE)-induced Sprague-Dawley rats. HBECs were transfected with small interfering RNA (siRNA) targeting Wnt5a or Ror2 and subsequently stimulated with PM2.5.The secretion of IL-6, IL-8 and IL-1β was assessed by ELISAs, and the expression of Wnt5a/Ror2 signaling were assessed by RT-PCR and Western blotting. Results Both Wnt5a and Ror2 protein were increased in the lung of MVE-induced rats. HBECs exposed to PM2.5 for 24 h significantly upregulated Wnt5a and Ror2 expression and subsequently promoted the nuclear translocation of NF-κB, which increased the production of IL-1β, IL-6 and IL-8. Wnt5a siRNA prevented these outcomes. Wnt5a antagonist (BOX5) also prevented inflammatory effects. Furthermore, Ror2 siRNA blocked the NF-κB activity and inhibited the release of IL-6, IL-8 and IL-1β from PM2.5-exposed HBECs. Conclusion PM2.5 induces the secretion of IL-6, IL-8 and IL-1β in HBECs via the Wnt5a/Ror2 signaling, demonstrating a novel mechanism for PM2.5-associated airway inflammation.

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“…HMGB1 and its cognate receptor RAGE were both induced in human bronchial epithelial cells and in the murine airway in response to PM 2.5 exposure. HMGB1 binding further activated TGF-β1 and PDGF release, providing strong evidence that HMGB1 is a mediator of PM 2.5 -induced EMT (Zou et al, 2018). Increased Shh expression activated downstream Shh/Gli1 signal transduction and further enhanced Snail expression as well as cell migration after low dose PM 2.5 exposure to human bronchial smooth muscle cells (Ye et al, 2018).…”

Section: Potential Mechanisms Of Pm25-induced Epithelial-mesenchymalmentioning

confidence: 95%

PM2.5, Fine Particulate Matter: A Novel Player in the Epithelial-Mesenchymal Transition?

Ding

Deng

2019

Front. Physiol.

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Epithelial-mesenchymal transition (EMT) refers to the conversion of epithelial cells to mesenchymal phenotype, which endows the epithelial cells with enhanced migration, invasion, and extracellular matrix production abilities. These characteristics link EMT with the pathogenesis of organ fibrosis and cancer progression. Recent studies have preliminarily established that fine particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) is correlated with EMT initiation. In this pathological process, PM2.5 particles, excessive reactive oxygen species (ROS) derived from PM2.5, and certain components in PM2.5, such as ions and polyaromatic hydrocarbons (PAHs), have been implicated as potential EMT mediators that are linked to the activation of transforming growth factor β (TGF-β)/SMADs, NF-κB, growth factor (GF)/extracellular signal-regulated protein kinase (ERK), GF/phosphatidylinositol 3-kinase (PI3K)/Akt, wingless/integrated (Wnt)/β-catenin, Notch, Hedgehog, high mobility group box B1 (HMGB1)-receptor for advanced glycation end-products (RAGE), and aryl hydrocarbon receptor (AHR) signaling cascades and to cytoskeleton rearrangement. These pathways directly and indirectly transduce pro-EMT signals that regulate EMT-related gene expression in epithelial cells, finally inducing the characteristic alterations in morphology and functions of epithelia. In addition, novel associations between autophagy, ATP citrate lyase (ACLY), and exosomes with PM2.5-induced EMT have also been summarized. However, some debates and paradoxes remain to be consolidated. This review discusses the potential molecular mechanisms underlying PM2.5-induced EMT, which might account for the latent role of PM2.5 in cancer progression and fibrogenesis.

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PM2.5 Induced the Expression of Fibrogenic Mediators via HMGB1-RAGE Signaling in Human Airway Epithelial Cells

Cited by 18 publications

References 22 publications

Airborne Particulates Affect Corneal Homeostasis and Immunity

Airborne Particulates Affect Corneal Homeostasis and Immunity

<p>PM2.5 Induces the Expression of Inflammatory Cytokines via the Wnt5a/Ror2 Pathway in Human Bronchial Epithelial Cells</p>

PM2.5, Fine Particulate Matter: A Novel Player in the Epithelial-Mesenchymal Transition?

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