Dataset Information

Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages.

ABSTRACT: BACKGROUND:Airway epithelial cells and alveolar macrophages (AMs) are the first line of defense in the lung during infection. Toll-like receptor (TLR) agonists have been extensively used to define the regulation of inflammation in these cells. However, previous studies were performed in non-paired airway epithelial cells and AMs. The major goal of our study was to compare the pro- and anti-inflammatory responses of paired human primary airway epithelial cells and AMs to TLR3 and TLR4 agonists. METHODS:Tracheobronchial epithelial cells (TBEC) and AMs from four smokers and four non-smokers without lung disease were cultured with or without Poly(I:C) (PIC) (a TLR3 agonist) or LPS (a TLR4 agonist) for 4, 24 and 48 h. The immune responses of paired cells were compared. RESULTS:TBEC and AMs showed stronger pro-inflammatory cytokine (e.g., IL-8) responses to PIC and LPS, respectively. TLR3 and TLR4 mRNA levels were similar in non-stimulated TBEC and AMs. However, PIC stimulation in AMs led to sustained up-regulation of the immune negative regulators Tollip and A20, which may render AMs less sensitive to PIC stimulation than TBEC. Unlike AMs, TBEC did not increase NF-?B activation after LPS stimulation. Interestingly, smoking status was correlated with less TLR3 and IRAK-M expression in non-stimulated TBEC, but not in AMs. PIC-stimulated TBEC and LPS-stimulated AMs from smokers vs. non-smokers produced more IL-8. Finally, we show that expression of A20 and IRAK-M is strongly correlated in the two paired cell types. CONCLUSIONS:By using paired airway epithelial cells and AMs, this study reveals how these two critical types of lung cells respond to viral and bacterial pathogen associated molecular patterns, and provides rationale for modulating immune negative regulators to prevent excessive lung inflammation during respiratory infection.

SUBMITTER: Mubarak RA

PROVIDER: S-EPMC6020222 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages.

Mubarak Reem Al RA Roberts Nicole N Mason Robert J RJ Alper Scott S Chu Hong Wei HW

Respiratory research 20180625 1

<h4>Background</h4>Airway epithelial cells and alveolar macrophages (AMs) are the first line of defense in the lung during infection. Toll-like receptor (TLR) agonists have been extensively used to define the regulation of inflammation in these cells. However, previous studies were performed in non-paired airway epithelial cells and AMs. The major goal of our study was to compare the pro- and anti-inflammatory responses of paired human primary airway epithelial cells and AMs to TLR3 and TLR4 ago ...[more]

PMID: 29940963

Similar Datasets

Project description:Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air-liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Dataset Information

Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages.

Publications

Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets