Sex differences in idiopathic pulmonary fibrosis (IPF) suggest a protective role for estrogen (E2); however, mechanistic studies in animal models have produced mixed results. Reports using cell lines have investigated molecular interactions between transforming growth factor beta1 (TGF-β1) and estrogen receptor (ESR) pathways in breast, prostate, and skin cells, but no such interactions have been described in human lung cells. To address this gap in the literature, we investigated a role for E2 in modulating TGF-β1-induced signaling mechanisms and identified novel pathways impacted by estrogen in bronchial epithelial cells. We investigated a role for E2 in modulating TGF-β1-induced epithelial to mesenchymal transition (EMT) in bronchial epithelial cells (BEAS-2Bs) and characterized the effect of TGF-β1 on ESR mRNA and protein expression in BEAS-2Bs. We also quantified mRNA expression of ESRs in lung tissue from individuals with IPF and identified potential downstream targets of E2 signaling in BEAS-2Bs using RNA-Seq and gene set enrichment analysis. E2 negligibly modulated TGF-β1-induced EMT; however, we report the novel observation that TGF-β1 repressed ESR expression, most notably estrogen receptor alpha (ESR1). Results of the RNA-Seq analysis showed that TGF-β1 and E2 inversely modulated the expression of several genes involved in processes such as extracellular matrix (ECM) turnover, airway smooth muscle cell contraction, and calcium flux regulation. We also report that E2 specifically modulated the expression of genes involved in chromatin remodeling pathways and that this regulation was absent in the presence of TGF-β1. Collectively, these results suggest that E2 influences unexplored pathways that may be relevant to pulmonary disease and highlights potential roles for E2 in the lung that may contribute to sex-specific differences.

Airborne exposure to nanomaterials from unintended occupational or environmental exposures or as a consequence of product use may lead to adverse health effects. Numerous studies have focused on single-walled carbon nanotubes (SWCNTs) and their ability to cause pulmonary injury related to fibrosis, and cancer; however few studies have addressed their impact on infectious agents, particularly viruses that are known for causing severe disease. Here we have demonstrated the ability of pristine SWCNTs of diverse electronic structure to increase the susceptibility of small airway epithelial cells (SAEC) to pandemic influenza A H1N1 infection and discerned potential mechanisms of action driving this response. Small airway epithelial cells (SAEC) were exposed to three types of SWCNTs with varying electronic structure (SG65, SG76, CG200) followed by infection with A/Mexico/4108/2009 (pH1N1). Cells were then assayed for viral infectivity by immunofluorescence and viral titers. We quantified mRNA and protein levels of targets involved in inflammation and anti-viral activity (INFβ1, IL-8, RANTES/CCL5, IFIT2, IFIT3, ST3GAL4, ST6GAL1, IL-10), localized sialic acid receptors, and assessed mitochondrial function. Hyperspectral imaging analysis was performed to map the SWCNTs and virus particles in fixed SAEC preparations. We additionally performed characterization analysis to monitor SWCNT aggregate size and structure under biological conditions using dynamic light scattering (DLS), static light scattering (SLS). Based on data from viral titer and immunofluorescence assays, we report that pre-treatment of SAEC with SWCNTs significantly enhances viral infectivity that is not dependent on SWCNT electronic structure and aggregate size within the range of 106 nm – 243 nm. We further provide evidence to support that this noted effect on infectivity is not likely due to direct interaction of the virus and nanoparticles, but rather a combination of suppression of pro-inflammatory (RANTES) and anti-viral (IFIT2, IFIT3) gene/protein expression, impaired mitochondrial function and modulation of viral receptors by SWCNTs. Results of this work reveal the potential for SWCNTs to increase susceptibility to viral infections as a mechanism of adverse effect. These data highlight the importance of investigating the ability of carbon-nanomaterials to modulate the immune system, including impacts on anti-viral mechanisms in lung cells, thereby increasing susceptibility to infectious agents.

Previous studies indicate that exposure of fish to pristine single-walled carbon nanotubes (SWCNTs) by oral gavage, causes no overt toxicity, and no appreciable absorption has been observed. However, in the environment, SWCNTs are likely to be present in dietary sources, which may result in differential impacts on uptake and biological effects. Additionally, the potential of these materials to sorb nutrients (proteins, carbohydrates, and lipids) while present in the gastrointestinal (GI) tract may lead to nutrient depletion conditions that impact processes such as growth and reproduction. To test this phenomenon, fathead minnows were fed a commercial diet either with or without SWCNTs for 96 h. Tracking and quantification of SWCNTs using near-infrared fluorescence (NIRF) imaging during feeding studies showed the presence of food does not facilitate transport of SWCNTs across the intestinal epithelia. Targeting genes shown to be responsive to nutrient depletion (peptide transporters, peptide hormones, and lipases) indicated that pept2, a peptide transporter, and cck, a peptide hormone, showed differential mRNA expression by 96 h, a response that may be indicative of nutrient limitation. The results of the current study increase our understanding of the movement of SWCNTs through the GI tract, while the changes in nutrient processing genes highlight a novel mechanism of sublethal toxicity in aquatic organisms.

Fish vitellogenin synthesized and released from the liver of oviparous animals is taken up into oocytes by the vitellogenin receptor. This is an essen

The agricultural crop sector in the United States depends on migrant, seasonal, and immigrant farmworkers. As an ethnic minority group in the U.S. with little access to health care and a high level of poverty, farmworkers face a combination of adverse living and workplace conditions, such as exposure to high levels of air pollution, that can place them at a higher risk for adverse health outcomes including respiratory infections. This narrative review summarizes peer-reviewed original epidemiology research articles (2000–2020) focused on respirable dust exposures in the workplace and respiratory illnesses among farmworkers. We found studies (n = 12) that assessed both air pollution and respiratory illnesses in farmworkers. Results showed that various air pollutants and respiratory illnesses have been assessed using appropriate methods (e.g., personal filter samplers and spirometry) and a consistent pattern of increased respiratory illness in relation to agricultural dust exposure. There were several gaps in the literature; most notably, no study coupled occupational air exposure and respiratory infection among migrant, seasonal and immigrant farmworkers in the United States. This review provides an important update to the literature regarding recent epidemiological findings on the links between occupational air pollution exposures and respiratory health among vulnerable farmworker populations.