miR-338-3p inhibits autophagy in a rat model of allergic rhinitis after PM2.5 exposure through AKT/mTOR signaling by targeting UBE2Q1.

Exposure to fine particulate matter (PM2.5) increases the incidence of allergic rhinitis (AR). microRNA (miRNA) can regulate cell proliferation, invasion and apoptosis. However, the mechanism of miR-338-3p in mediating PM2.5-induced autophagy in AR animal models remains unknown. To explore the mechanism of miR-338-3p in PM2.5-induced autophagy in AR, the human nasal epithelium cells and AR model exposed to PM2.5 were deployed. The results showed that miR-338-3p was down-regulated in both nasal mucosa of PM2.5-exacerbated AR rat models and PM2.5-treated RPMI-2650 cells. Forced expression of miR-338-3p could inhibit autophagy in vitro. miR-338-3p specifically bound to UBE2Q1 3'-untranslated region (3' UTR) and negatively regulated its expression. Overexpression of UBE2Q1 attenuated the inhibitory effects of miR-338-3p on PM2.5-induced autophagy of RPMI-2650 cells through AKT/mTOR pathway. Moreover, our in vivo study found that after administration of agomiR-338-3p in AR rats model, the expression of autophagy-related proteins decreased and nasal symptoms alleviated. In conclusion, this study revealed that miR-338-3p acts as an autophagy suppressor in PM2.5-exacerbated AR by directly targeting UBE2Q1 and affecting AKT/mTOR pathway.

Effect of PM2.5 on MicroRNA Expression and Function in Nasal Mucosa of Rats With Allergic Rhinitis.

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.

T-helper type 1-T-helper type 2 shift and nasal remodeling after fine particulate matter exposure in a rat model of allergic rhinitis.

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.

[Characteristics of re-suspended road dust and its significant effect on the airborne particulate pollution in Beijing].

The re-suspended road dust samples from 53 sites that could cover basically the entire Beijing in summer, and aerosol samples from three representative sites in Beijing in four seasons were collected to study concentrations and spatial variations of elements and ions in resuspended road dust and its contribution to the air-borne particulate pollution. Ca, S, Cu, Zn, Ni, Pb and Cd were main pollution elements, and Ca2+, SO4(2-), Cl-, K+, Na+ and NO3- were major ions in re-suspended road dust. Al, Ti, Sc, Co and Mg in re-suspended road dust were mainly originated from crustal source, while Cu, Zn, Ni and Pb were mainly originated from traffic emissions and coal burning, and Fe, Mn and Cd were mainly from industrial emissions and coal combustion. Ca2+ and SO4(2-) mainly came from construction activities, construction materials and secondary gas-particle conversions, Cl- and Na+ were derived from industrial wastewater disposal and chemical industrial emissions, and NO3- and K+ were from vehicle emissions, photochemical reactions of NO,, biomass and vegetable burning. The contribution of mineral aerosol from inside Beijing to the total mineral aerosols was 30% in spring of 2002, 70% in summer of 2002, 80% in autumn of 2003, 20% in winter of 2002. The pollution levels of some major pollution species, Ca, S, Cu, Zn, Ni, Pb, Fe, Mn, and Cd in resuspended road dust reached 76%, 87%, 75%, 80%, 82%, 90%, 45%, 51%, and 94%, respectively, and their contributions to the related elements in PM10 were 20%-45%, 5%-18%, 4%-50%, 2%-46%, 4%-52%, 5%-20%, 30%-60%, 20%-40% and 2%-25%. Re-suspended road dust from the traffic and construction activities is one of the major sources of the air-born particulate pollution in Beijing.

Characteristics and seasonal variations of PM2.5, PM10, and TSP aerosol in Beijing.

OBJECTIVE: To investigate the seasonal characteristics and the sources of elements and ions with different sizes in the aerosols in Beijing. METHODS: Samples of particulate matters (PM2.5), PM10, and total suspended particle (TSP) aerosols were collected simultaneously in Beijing from July 2001 to April 2003. The aerosol was chemically characterized by measuring 23 elements and 18 water-soluble ions by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and ion chromatography (IC), respectively. RESULTS: The samples were divided into four categories: spring non-dust, spring dust, summer dust, and winter dust. TSP, PM10, and PM2.5 were most abundant in the spring dust, and the least in summer dust. The average mass ratios of PM > 10, PM2.5-10, and PM2.5 to TSP confirmed that in the spring dust both the large coarse (PM > 10) and fine particles (PM2.5) contributed significantly in summer PM2.5, PM2.5-10, and PM > 10 contributed similar fractions to TSP, and in winter much PM2.5. The seasonal variation characteristics of the elements and ions were used to divide them into four groups: crustal, pollutant, mixed, and secondary. The highest levels of crustal elements, such as Al, Fe, and Ca, were found in the dust season, the highest levels of pollutant elements and ions, such as As, F-, and Cl-, were observed in winter, and the highest levels of secondary ions (SO4(2-), NO3-, and NH4+) were seen both in summer and in winter. The mixed group (Eu, Ni, and Cu) showed the characteristics of both crustal and pollutant elements. The mineral aerosol from outside Beijing contributed more than that from the local part in all the reasons but summer, estimated using a newly developed element tracer technique.

Determination of polynuclear aromatic hydrocarbons in aerosol by solid-phase extraction and gas chromatography-mass spectrum.

The optimum procedures for clean up aerosols in silica solid-phase extraction (SPE) cartridge prior to the analysis of polynuclear aromatic hydrocarbons (PAHs) by gas chromatography-mass spectrum (GC-MS) in selected ion monitoring detection mode have been investigated. The silica SPE cartridge is activated by dichloromethane and hexane, and then dried up by vacuum in SPE instrument for about 5 min. The sample volume loaded on the cartridge is 3 ml and after loading the sample the cartridge was dried in vacuum for 5 min. The PAHs were eluted from the cartridge by 3 ml 20% dichloromethane in hexane. The flow-rate of sample loading and eluting was controlled in about 1 ml min(-1). The aerosols collected on the campus of Beijing Normal University from August 2001 to July 2002 have been processed with these optimum procedures and 16 EPA priority pollution PAHs in the aerosols have been quantitatively determined.