PM2.5 organic extract mediates inflammation through the ERβ pathway to contribute to lung carcinogenesis in vitro and vivo

Luo, Fei; Guo, Huaqi; Yu, Hengyi; Li, Yan; Feng, Yuanming; Wang, Yan

doi:10.1016/j.chemosphere.2020.127867

Cited by 31 publications

(18 citation statements)

References 53 publications

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“…According to our findings, ERβ was expressed in our in vitro model of HepG2 cells and could be modulated by GEN or PHTPP. This modulation pattern was inconsistent with several other studies that also showed increased ERβ protein levels by GEN [44,45] or decreased ERβ protein levels by PHTPP [46]. The mechanisms of protein expression change by antagonists remains unclear and might be explained due to a complex form of antagonist-ER depending on a ligand binding which shows a tendency for degradation [47,48].…”

Section: Discussioncontrasting

confidence: 83%

Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

et al. 2021

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Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor β (ERβ) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERβ antagonist were treated with HepG2 cells. Results showed that 25 μM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid β-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 μM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERβ. In conclusion, GEN improved hepatic lipid metabolism by activating ERβ and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERβ on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.

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Section: Discussioncontrasting

confidence: 83%

Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

et al. 2021

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“…As shown in Fig. 1 and our previous report (Luo et al 2020), during the entire period of the animal experiment, there was no obvious difference in the changes of body weight between groups of female or male mice.…”

Section: Changes In Body Weightsupporting

confidence: 71%

“…An inhalation exposure system (Shanghai Raymain Information Technology Co., Ltd.) was used for the animal experiment, which can real-time monitor dynamic parameters in the exposure chamber, including the concentration of Po aerosols, temperature, humidity, O 2 and CO 2 concentration. The experimental procedure has been described in our previous article (Luo et al 2020), with additional male mice in the present study. Brie y, the female and male mice were respectively divided randomly into three groups (8 mice/group): a, Control groups; b, Po groups; c, Po + PHTPP groups.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study has proved that Po can induce pulmonary in ammation in female mice (Luo et al 2020). We further included male mice in the present experiment.…”

Section: The Effects Of Po On Pulmonary In Ammation In Female and Male Micementioning

confidence: 96%

“…The detailed method of obtaining BALF has been described in a previous article (Luo et al 2020). Brie y, BALF were centrifuged at 1000×g for 5 min at 4°C.…”

Section: Preparation and Cell Counts Of Bronchoalveolar Lavage Fluid (Balf)mentioning

confidence: 99%

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The Role of Estrogen Receptor β in PM2.5 Organic Extract-Induced Pulmonary Inflammation in Female and Male Mice

Guo

Feng

et al. 2022

Preprint

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Automobile exhaust is one of the main sources of PM2.5 in urban areas, and traffic-originated PM2.5 organic extract (Po) can promote inflammation in different organs, especially in the lung. In addition, sex differences were reported in many inflammatory diseases, but the triggering factors of sex differences in inflammatory responses are still unclear. In this study, we investigated the effects of Po exposure on pulmonary inflammatory responses and evaluated the role of sex in this process. Mice were exposed to 100 µg/m3 Po for 12 weeks by an inhalation exposure system in a polycarbonate chamber. In Po-exposed mice, the lung histopathological analysis shown obvious inflammation, the cell numbers in bronchoalveolar lavage fluid (BALF) were significantly increased, and most inflammatory cytokines in BALF were upregulated. Factorial analysis of variance was carried out to investigate the interaction between sex and Po exposure in these effects. The results shown that the increase of inflammatory cell numbers and the fluctuation of cytokine levels (TNF-α, IL-5, and GRO/KC) in BALF induced by Po were significantly different between female and male mice. Notably, these differences were diminished while Po-exposed mice were injected with PHTPP, an ERβ antagonist (1 mg/kg, i.p.). We hypothesized that Po-induced inflammatory responses were different between female and male mice, and ERβ was involved in these processes. To our knowledge, this is the first investigation about the role of sex in Po-induced adverse effects. This study provided a theoretical basis for understanding the sex differences in the adverse effects of environmental pollutants.

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Induction of heme oxygenase‐1 antagonizes PM2.5‐induced pulmonary VEGFA expression through regulating HIF‐1α

Wen

et al. 2023

J Biochem & Molecular Tox

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Particulate matter (PM) 2.5 has long been regarded as a major risk factor of the respiratory system, which constitutes a threat to human health. Although the positive relationship between PM2.5 exposure and the development of respiratory diseases has been well established, limited studies investigate the intrinsic self‐protection mechanisms against PM2.5‐induced respiratory injuries. Excessive pulmonary inflammation served as a key pathogenic mechanism in PM2.5‐induced airway dysfunction, and we have previously shown that PM2.5 induced the production of vascular endothelial growth factor A (VEGFA) in the bronchial epithelial cells, which subsequently led to pulmonary inflammatory responses. In the current study, we found that PM2.5 also concurrently induced the expression of the stress‐responsive protein heme oxygenase‐1 (HO‐1) along with VEGFA in the bronchial epithelial cells both in vivo and in vitro. Importantly, knocking down of HO‐1 expression significantly increased the synthesis and secretion of VEGFA; while overexpression of HO‐1 showed the opposite effects, indicating that HO‐1 induction can antagonize VEGFA production in the bronchial epithelial cells upon PM2.5 exposure. Mechanistically, HO‐1 inhibited PM2.5‐evoked VEGFA induction through modulating hypoxia‐inducible factor 1 alpha (HIF‐1α), which was the upstream transcriptional factor of VEGFA. More specifically, HO‐1 could not only inhibit HIF‐1α expression, but also suppress its transactivity. Taken together, our results suggested that HO‐1 was an intrinsic protective factor against PM2.5‐induced pulmonary VEGFA production with a mechanism relating to HIF‐1α, thus providing a potential treatment strategy against PM2.5 triggered airway injuries.

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PM2.5 organic extract mediates inflammation through the ERβ pathway to contribute to lung carcinogenesis in vitro and vivo

Cited by 31 publications

References 53 publications

Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

The Role of Estrogen Receptor β in PM2.5 Organic Extract-Induced Pulmonary Inflammation in Female and Male Mice

Induction of heme oxygenase‐1 antagonizes PM2.5‐induced pulmonary VEGFA expression through regulating HIF‐1α

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