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To explore the role and mechanism of ferroptosis in exacerbating airway inflammation in asthmatic mice exposed to traffic-related PM2.5.
Fifty BALB/c mice were randomly divided into five groups: saline (NS), asthma (ovalbumin, OVA), and OVA combined with low, medium, and high exposure to traffic-derived PM2.5 (1.8, 3.6, and 7.2 mg/kg·bw, respectively). The levels of IL-6 and TNF-α in lung tissue were measured using ELISA kits. The concentrations of reduced glutathione (GSH), malondialdehyde (MDA), and Fe2+ in lung homogenate supernatants were assessed by colorimetry. Protein expressions of prostaglandin-endoperoxide synthase 2 (PTGS2), acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), tumor protein p53 (p53), phospho-p53 (p-p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), and arachidonate 15-lipoxygenase (ALOX15) were detected using western blot. mRNA expressions of PTGS2, ACSL4, GPX4, p53, SAT1, and ALOX15 were examined by qRT-PCR. One-way ANOVA was used for multi-group data comparison, followed by Tukey’s HSD for further multiple comparisons.
PM2.5 exposure significantly increased IL-6 and TNF-α levels in asthmatic mouse lung tissues, especially in the high PM2.5 exposure group (FIL-6=17.910, P<0.001; FTNF-α=5.414, P<0.05). All PM2.5 exposure groups showed a reduction in GSH, most notably in the high exposure group (FGSH=13.560, P<0.001). MDA and Fe2+ levels were significantly higher in the medium and high PM2.5 groups compared to the OVA group (FMDA=55.230, P<0.001; FFe=17.660, P<0.001). PM2.5 exposure also elevated the protein and mRNA expressions of PTGS2, ACSL4, and ALOX15, while reducing GPX4 expression. The protein and mRNA expression levels of p53, SAT1, and ALOX15 showed a clear dose-response to PM2.5, with p-p53 following a similar trend as p53 protein expression.
Traffic-related PM2.5 may induce ferroptosis in the lungs of asthmatic mice and exacerbate asthma inflammation through the p53/SAT1/ALOX15 pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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