Fossil and non-fossil sources of the carbonaceous component of PM2.5 in forest and urban areas.

Atmospheric particulate matter (PM2.5) can damage human health. Biogenic organic compounds emitted from trees may increase the concentration of PM2.5 via formation of secondary aerosols. Therefore, the role of biogenic emissions in PM2.5 formation and the sources of PM2.5 need to be investigated. Dual carbon isotope and levoglucosan analyses are powerful tools to track the sources of total carbon (TC) in PM2.5. We collected a total of 47 PM2.5 samples from 2019 to 2020 inside a pine forest and in urban areas in South Korea. The average δ13C and Δ14C of TC in PM2.5 at the Taehwa Research Forest (TRF) were - 25.7 and - 380.7‰, respectively, which were not significantly different from those collected at Seoul National University (SNU) in urban areas. Contribution of fossil fuel, C3-, and C4- plants to carbonaceous component of PM2.5 were 52, 27, and 21% at SNU, whereas those were 46, 35, and 19% at TRF, respectively. The biomass burning tracer, levoglucosan, was most abundant in winter and correlated with the contribution of C4 plants derived carbon. Results indicate that biogenic aerosols emitted from trees is less likely to be an important source of PM2.5 and that trees can act as a bio-filter to reduce PM2.5.

Properties of river organic carbon affected by wastewater treatment plants.

Tracking the sources of organic carbon (OC) is critical not only for understanding riverine carbon dynamics but also for providing management options to improve water quality. We collected water samples from upland forest streams to the mainstream Geumho River (GHR) of South Korea, which included a variety of wastewater treatment plants (WWTP) effluents. We analyzed the concentrations, optical properties, and dual carbon isotope ratios of these samples to identify the sources of OC. Dissolved organic carbon (DOC) was the dominant form of OC in the GHR compared to particulate organic carbon (POC), as the former accounted for 87 % of OC. The concentrations of DOC and POC ranged from 1.2 to 11.2 mg L-1 and from 0 and 3.6 mg L-1, respectively, aside from the livestock WWTP effluent. Dominant fluorescence components were terrestrial humic substances in upper reaches whereas protein-like materials in lower reaches of the GHR whose watershed includes a large city with many WWTPs. Significantly lower Δ14C-DOC and Δ14C-POC were observed in industrial WWTP effluents than the other sites due to the contribution of fossil OC. Livestock WWTP effluents had higher δ13C-DOC and δ13C-POC than most of the sites, possibly due to the animal feed derived from C4 plants such as corn. Fossil OC contributed 29-52 % of [DOC] and 36-56 % of [POC] from industrial WWTP effluents, whereas C4-plants derived OC contributed about half of [DOC] and [POC] from a livestock WWTP effluent. The results suggest that anthropogenic sources of organic carbon could alter river carbon dynamics, and that caution is needed when we interpret isotope ratios of riverine organic carbon, particularly when the river passes through highly populated areas wherein WWTP effluents are large.

High dissolved organic radiocarbon in precipitation during winter and its implication on the carbon cycle.

Radiocarbon (14C) analysis is a powerful tool for tracing carbon in the global carbon cycle. Precipitation is a component of the global carbon cycle through which dissolved organic carbon (DOC) enters terrestrial and aquatic ecosystems from the atmosphere. In previous studies, the Δ14C of DOC in rain or snow was negative indicating an input of relatively old organic carbon including fossil fuels, with only a few positive values up to +108‰ showing the signal of recent photosynthesis. However, here we report surprisingly high Δ14C-DOC in bulk precipitation, more than 1000‰ in Seoul, South Korea, especially when the Northwesterly wind blows during winter. In contrast, Δ14C of particulate organic carbon (POC) in bulk precipitation was negative, indicating that the sources of POC and DOC were different. Although the sources of the high Δ14C-DOC are not clear and future studies on them are required, the relatively high Δ14C-DOC in a nearby headwater stream suggests that precipitation DOC has the potential to affect the local carbon cycle, and that stream DOC derived from terrestrial ecosystems could be older than previously thought. The analysis of Δ14C-DOC of precipitation in many other locations is necessary to understand how long carbon stays in terrestrial ecosystems.

Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma.

BACKGROUND AND OBJECTIVE: The neurotransmitter, 5-hydroxytryptamine, acts as an immunomodulator by stimulating the release of inflammatory cytokines and regulating the function of dendritic cells and monocytes. The 5-hydroxytryptamine receptor 4 (HTR4) gene is located in a region previously linked to an increased risk of asthma and atopy. The aim of this study was to investigate the association between HTR4 and asthma. METHODS: Thirty-two single nucleotide polymorphisms (SNP) in HTR4 were investigated by direct sequencing of 24 DNA samples from unrelated Korean subjects. RESULTS: The 32 genetic variants comprised 22 intronic SNP, two SNP in the 3'-untranslated region (exon 7) and eight SNP in the 3'-downstream region. Logistic regression analysis showed that two intronic polymorphisms were significantly associated with the risk of asthma. Two minor HTR4 alleles, +142828G>A and +122769G>A, occurred at significantly higher frequencies in the asthmatic group than in the healthy control group (49.59% vs 42.29%, P=0.003, and 47.99% vs 40.35%, P=0.008, respectively), and these differences remained significant after correction for multiple testing (P=0.05, dominant mode of inheritance; and P=0.03, dominant mode, respectively). Haplotype analysis revealed three haplotype blocks. The frequency of haplotype 1 in block 2 was significantly higher in asthmatics (P=0.003, dominant mode), whereas the frequency of haplotype 4 in block 3 was significantly lower in asthmatics (P=0.0009, dominant mode). CONCLUSIONS: SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma.

KIF3A, a cilia structural gene on chromosome 5q31, and its polymorphisms show an association with aspirin hypersensitivity in asthma.

INTRODUCTION: The kinesin family number 3A (KIF3A) gene on the human chromosomal 5q31-33 region, which is known as a susceptibility locus for immune diseases including asthma, plays a crucial role in generation of cilia. RESULTS: A treatment with aspirin in the human bronchial epithelial cells increased the mRNA expression level of KIF3A compared to that of the untreated control (P ≤ 0.01), and nasal polyp epithelia from aspirin-intolerant asthma (AIA) patients also showed a higher expression of KIF3A protein than aspirin-tolerant asthma controls. Further logistic analyses revealed that most polymorphisms of KIF3A were significantly associated with AIA (P = 0.0004-0.02; P(corr) = 0.004-0.04) and the decline of forced expiratory volume at 1 s (FEV(1))% by aspirin provocation (P = 0.004-0.04; P(corr) = 0.03). DISCUSSION: Our findings suggest that the KIF3A gene and/or its polymorphisms might have a susceptibility effect on AIA, providing a new step toward controlling aspirin intolerance in asthmatics.

Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES: To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. METHODS: Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. MEASUREMENTS AND MAIN RESULTS: Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006-0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control animals. Immunohistochemical analysis showed positive staining on intraalveolar macrophages and epithelial cells of the lungs. Intranasal treatment with Apo A-I protein reduced the bleomycin-induced increases in number of inflammatory cells and collagen deposition in sham-treated mice in a dose-dependent manner. CONCLUSIONS: Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.

Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis.

BACKGROUND: No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production. METHODS: BMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed. RESULTS: Nitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1beta, IL-6, TNF-alpha, TGF-beta and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury. CONCLUSION: Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.

Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma.

BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are the nuclear hormone receptor superfamily of ligand-activated transcriptional factors. PPAR-gamma (PPARG) activation downregulates production of Th2 type cytokines and eosinophil function. Additionally, treatment with a synthetic PPARG ligand can reduce lung inflammation and IFN-gamma, IL-4, and IL-2 production in experimental allergic asthma. In patients with asthma, PPARG gene expression is known to be associated with the airway inflammatory and remodeling responses. Thus, genetic variants of PPARG may be associated with the development of asthma. METHODS: We genotyped two single nucleotide polymorphisms on the PPARG gene, +34C>G (Pro12Ala) and +82466C>T (His449His), in Korean subjects (839 subjects with asthma and 449 normal controls). RESULTS: Association analysis using logistic regression analysis showed that +82466C>T and haplotypes 1(CC) and 2(CT) were associated with the development of asthma (p=0.01-0.04). The frequency of PPARG-ht2 was significantly lower in the patients with asthma compared to the normal controls in codominant and dominant models (p=0.01, p(corr)=0.03 and p=0.02, p(corr)=0.03, respectively). Conversely, the frequency of PPARG-ht1 was significantly higher in the patients with asthma compared to the normal controls in the codominant model [p=0.04, OR: 1.27 (1.01-1.6)]. In addition, the rare allele frequency of +82466C>T was significantly lower in patients with asthma in comparison to normal controls in the codominant model (OR: 0.78, p=0.04). Thus, polymorphism of the PPARG gene may be linked to an increased risk of asthma development.