ABSTRACT
BACKGROUND: Particulate matter 2.5 (PM2.5) refers to particulate matter with aerodynamic equivalent diameter less than or equal to 2.5 µm, which is an important component of air pollution. PM2.5 aggravates allergic rhinitis (AR) and promotes AR nasal mucosa inflammation. Therefore, the influence of PM2.5 inhalation exposure on microRNA (miRNA) expression profiles and function in the nasal mucosa of AR rats was investigated. METHODS: Female Sprague Dawley rats were distributed randomly to 2 groups: AR model PM2.5 exposure group (ARE group) and AR model PM2.5-unexposed control group (ARC group). The rats of ARE group were made to inhale PM2.5 at a concentration of 200 µg/m3, 3 h/day, for 30 days. miRNA expression profiles of the nasal mucosa from both groups were determined using an miRNA gene chip and were verified by quantitative real-time PCR (qRT-PCR). Gene function enrichment analysis was performed using bioinformatics analysis. RESULTS: The ARE group revealed 20 significantly differentially expressed miRNAs, including 4 upregulated and 16 downregulated miRNAs (fold change > 1.5 or < 0.66, P < .05). Of these, 9 selected miRNAs were verified by qRT-PCR, and the results of 8 miRNAs were in accordance with the miRNA gene chip results, with highly positive correlation (r = .8583, P = .0031). Numerous target genes of differentially expressed miRNAs were functionally enriched in high-affinity immunoglobulin E receptor signaling, ErbB signaling, mucin O-glycans biosynthesis, transforming growth factor ß signaling, mitogen-activated protein kinase signal transduction, phosphatidylinositol signaling, mucopolysaccharide biosynthesis, mammalian target of rapamycin signaling, T cell receptor signaling, Wnt signaling, chemokine signal transduction, and natural killer cell-mediated cytotoxicity pathways. CONCLUSIONS: PM2.5 causes significant changes in miRNA expression in the nasal mucosa of AR rats. miRNA plays an important role in regulating PM2.5 effects in AR rat biological behavior and mucosal inflammation. This study provides a theoretical basis for the prevention and treatment of AR from the effects of environmental pollution on the gene regulation mechanism.
Subject(s)
Environmental Exposure/adverse effects , Inflammation/genetics , MicroRNAs/genetics , Nasal Mucosa/physiology , Particulate Matter/adverse effects , Rhinitis, Allergic/genetics , Animals , Female , Gene Expression Profiling , Humans , Immunoglobulin E/genetics , Immunoglobulin E/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Signal TransductionABSTRACT
BACKGROUND: Exposure to fine particulate matter (particulate matter ≤2.5 µm [PM2.5]) increases the risk of allergic rhinitis (AR), but the underlying mechanisms remains unclear. Thus, we investigated the roles of T-helper (Th)1-Th2 cytokines and nasal remodeling after ambient PM2.5 exposure in a rat model of AR. METHODS: Female Sprague-Dawley rats were randomized into six groups: a negative control group, a group of healthy rats exposed to 3000 µg/m3 PM2.5, an ovalbumin (OVA) induced AR model, and three PM2.5-exacerbated AR groups exposed to three different concentrations (200, 1000, and 3000 µg/m3) of PM2.5 for 30 days via inhalation. Nasal symptoms, levels of Th1-Th2 cytokines, the degree of eosinophilia in nasal lavage fluid (NLF), and the messenger RNA (mRNA) expressions of transcription factors GATA-3 and T-bet in the nasal mucosa were measured in each individual rat. Hyperplasia of globet cells and collagen deposition were examined by histology. RESULTS: PM2.5 significantly increased the number of sneezes and nasal rubs in rats with AR. PM2.5 also significantly decreased interferon gamma and increased interleukin (IL) 4 and IL-13 expressions as well as the number of eosinophils in NLF. The mRNA expression of GATA-3 in the nasal mucosa of rats with AR was upregulated by PM2.5, whereas T-bet was significantly downregulated. Statistically significant differences in OVA-specific serum immunoglobulin E, goblet cell hyperplasia, collagen deposition, and transforming growth factor beta 1 levels were observed between the PM2.5-exacerbated AR groups and the AR model group. CONCLUSION: Analysis of our data indicated that an increase in the immune response with Th2 polarization and the development of nasal remodeling may be the immunotoxic mechanisms behind the exacerbation of AR after exposure to PM2.5.
