Comparison of the Effects of Bathing and the Dry Technique on the Skin Condition of Early Neonates: A Prospective Observational Study.

BACKGROUND: In Japan, neonates have typically been bathed in a bathtub immediately after birth because bathing is a custom for cleansing impurities. However, dry technique has been introduced into many institutions since 2000. There is little scientific evidence on the benefit or harmfulness of either method to neonatal skin, and consequently, opinion remains split on which method is superior. OBJECTIVE: The purpose of the present study was to determine whether bathing or the dry technique of cleaning is better in maintaining skin health in the early neonatal period. METHODS: Transepidermal water loss (TEWL) and skin pH, considered an index of skin barrier function, were measured in each group. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, which are inflammatory cytokines released by keratinocytes, were measured by skin blotting. RESULTS: TEWL and skin pH of neonates were lower with the dry technique than with bathing. The expression level of IL-6 and TNF-α in chest skin of neonates was higher with bathing than with the dry technique. CONCLUSION: These results suggest that the dry technique may maintain skin health better than bathing in the early neonatal period.

Effects of Fetal Exposure to Heat-Not-Burn Tobacco on Testicular Function in Male Offspring.

Several studies show that maternal conventional cigarette smoking during pregnancy has been associated with reduced sperm concentration in sons. The development of heat-not-burn (HnB) tobacco has gained a growing following. However, the effects of prenatal HnB tobacco smoking on male offspring are as yet unknown. Pregnant CD-1 mice were exposed to I-Quit-Ordinary-Smoking (IQOS) (HnB tobacco) aerosol from heat sticks, mainstream smoke from 3R4F (conventional cigarettes) or clean air, using a whole-body exposure system. Adult male offspring mice were divided into six groups: control (5- and 15-weeks-old offspring), IQOS (5 and 15-weeks-old) and 3R4F (5 and 15-weeks-old). Spermatogenesis, sperm characteristics, serum testosterone, and seminiferous tubule morphology were evaluated. Prenatal IQOS exposure increased abnormal seminiferous tubule morphology and decreased sperm production at 5 weeks, but 3R4F exposure did not. Prenatal exposure to IQOS aerosol delays sexual maturation of male offspring or adversely affects the male testicular function of the offspring more than smoke from a combustion cigarette.

Investigation of inflammation inducing substances in PM2.5 particles by an elimination method using thermal decomposition.

The substances associated with PM2.5-induced inflammatory response were investigated using an elimination method. PM2.5 were heated at temperatures of 120, 250, and 360°C. The results demonstrated microbial substances such as LPS and b-glucan, and chemicals including BaP, 1,2-NQ, and 9,10-PQ were reduced drastically in PM2.5 heated at 120°C. On the other hand, DBA, 7,12-BAQ, and BaP-1,6-Q were not noticeably reduced. Most of these substances had disappeared in PM2.5 heated at 250°C and 360°C. Metals (eg, Fe, Cu, Cr, Ni) in PM2.5 exhibited a slight thermo-dependent increase. RAW264.7 macrophages with or without NAC were exposed to unheated PM2.5, oxidative stress-related and unrelated inflammatory responses were induced. PM2.5-induced lung inflammation in mice is caused mainly by thermo-sensitive substances (LPS, b-glucan, BaP, 1,2-NQ, 9,10-PQ, etc.). Also, a slight involvement of thermo-resistant substances (DBA, 7,12-BAQ, BaP-1,6-Q, etc.) and transition metals was observed. The thermal decomposition method could assist to evaluate the PM2.5-induded lung inflammation.

Role of iron and oxidative stress in the exacerbation of allergic inflammation in murine lungs caused by urban particulate matter <2.5 µm and desert dust.

Simultaneous exposure of lipopolysaccharide (LPS) and urban particulate matter <2.5 µm (PM2.5) or desert dust exacerbated murine asthma. In the present study, the role of iron (Fe) contained in particles and oxidative stress was investigated using Fe chelator deferoxamine (DFO) and oxidative stress scavenger N-acetylcysteine (NAC) in a murine asthma model exacerbated by LPS + PM2.5 or LPS + Asian sand dust (ASD). When BALB/c mice were intratracheally challenged with ovalbumin (OVA) + LPS and either urban PM2.5 or ASD, LPS + PM2.5 and LPS + ASD caused exacerbation of OVA-induced lung eosinophilia along with T-helper 2 cytokine and eosinophil-relevant chemokine production in bronchoalveolar lavage fluid as well as the production of OVA-specific IgE in serum. LPS + PM2.5 with NAC tended to reduce the lung eosinophilia compared to the LPS + PM2.5 host, whereas LPS + PM2.5 with DFO did not reduce them. LPS + ASD with NAC moderately reduced the lung eosinophilia compared to the LPS + ASD host. LPS + ASD with DFO drastically reduced the lung eosinophilia compared to the LPS + ASD host. The concentration of Fe in urban PM2.5 and ASD were almost the same. However, the concentrations of trace metals Pb, Cu, As, Ni, Cr, Mo, Sb, Co, Se and Cd were greater in PM2.5 than in ASD. These results suggested that Fe and oxidative stress are at least partly involved in lung eosinophilia exacerbation caused by LPS + ASD. However, trace metals (except Fe) might also be involved in lung eosinophilia exacerbated by LPS + PM2.5.

Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway.

Nevertheless its mechanism has not been well explained yet, PM2.5 is recognized to exacerbate asthma. In the present study, the roles of toll-like receptor (TLR) 2, TLR4 and MyD88, in exacerbation of allergen-induced lung eosinophilia caused by urban PM2.5 was investigated. TLR2-, TLR4-, MyD88-deficient and WT BALB/c mice were intratracheally challenged with PM2.5 +/- ovalbumin (OVA) four times at 2-week intervals. PM2.5 increased neutrophil numbers and KC in bronchoalveolar lavage fluid and caused slight peribronchiolar inflammation in WT mice. However, these changes were attenuated, but not completely suppressed in gene-deficient mice, especially in MyD88-/- mice. In WT mice, PM2.5 + OVA exacerbated OVA-related lung eosinophilia. This exacerbation includes increase of IL-5, IL-13, eotaxin and MCP-3; infiltration of eosinophils into the airway submucosa; proliferation of goblet cells in the airway epithelium; and the production of antigen-specific IgE and IgG1 in serum. All these effects were stronger in TLR2-/- mice than in TLR4-/- mice. In MyD88-/- mice, this pro-inflammatory mediator-inducing ability was considerably weak and lung pathology was negligible. These results suggest that urban PM2.5 may exacerbate allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway. PM2.5-bound trace microbial elements, such as lipopolysaccharide may be a strong candidate for exacerbation of murine lung eosinophilia.

PM2.5-induced lung inflammation in mice: Differences of inflammatory response in macrophages and type II alveolar cells.

Particulate matter 2.5 (

Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory and immune responses.

Particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5 ) is generally composed of carbon nuclei associated with various organic carbons, metals, ions and biological materials. Among these components, polyaromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) and quinones have detrimental effects on airway epithelial cells and immunodisrupting effects, which leads to the exacerbation of respiratory allergies. The effects of PAHs and the carbon nuclei, separately as well as in combination, remain to be established. We investigated the effects of BaP, 9,10-phenanthroquinone (9,10-PQ), and 1,2-napthoquinone (1,2-NQ) and their combined effects with heated diesel exhaust particle (H-DEP) as carbon nuclei of typical PM2.5 . We exposed human airway epithelial cells (BEAS-2B), murine bone marrow-derived antigen-presenting cells (APCs), and murine splenocytes to BaP, 9,10-PQ, or 1,2-NQ in the presence and absence of H-DEP. Several important inflammatory cytokines and cell surface molecules were measured. PAHs alone did not have apparent cytotoxic effects on BEAS-2B, whereas combined exposure with H-DEP induced noticeable detrimental effects which mainly reflected the action of H-DEP itself. BaP increased CD86 expression as an APC surface molecule regardless of the presence or absence of H-DEP. None of the BaP, 9,10-PQ, or 1,2-NQ exposure alone or their combined exposure with H-DEP resulted in any significant activation of splenocytes. These results suggest that PAHs and carbon nuclei show additive effects, and that BaP with the carbon nuclei may contribute to exacerbations of allergic respiratory diseases including asthma by PM2.5 , especially via antigen-presenting cell activation.

Biological factor related to Asian sand dust particles contributes to the exacerbation of asthma.

Epidemiologic studies have revealed that Asian sand dust particles (ASDs) can affect respiratory and immune health represented by asthma. Factors responsible for the exacerbation of asthma remain unclear. The fungus Bjerkandera adusta (B.ad) and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) have been identified in ASDs collected from the atmosphere when an ASD event occurred. We investigated the effects of B.ad and BaP related to ASDs on respiratory and immune systems. Bone marrow-derived antigen-presenting cells (APCs) and splenocytes from atopic prone NC/Nga mice and human airway epithelial cells were exposed to the B.ad or to BaP in the presence and absence of heated-ASDs (H-ASDs). B.ad and BaP in both the presence and absence of H-ASDs increased the expression of cell surface molecules on APCs. H-ASDs alone slightly activated APCs. The expressions induced by B.ad were higher than those induced by BaP in the presence and absence of H-ASDs. There were no remarkable effects on the activation of splenocytes or the proinflammatory responses in airway epithelial cells. These results suggest that B.ad rather than BaP contributes to the exacerbation of asthma regardless of the presence or absence of sand particles, particularly by the activation of the immune system via APCs. Copyright © 2016 John Wiley & Sons, Ltd.

Differences in allergic inflammatory responses in murine lungs: comparison of PM2.5 and coarse PM collected during the hazy events in a Chinese city.

Urban particulate matter (PM) is associated with an increase in asthma. PM2.5 (

Effects of Fetal Exposure to Asian Sand Dust on Development and Reproduction in Male Offspring.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproduction in mice. However, the effects of fetal ASD exposure on male reproduction have not been investigated. The present study investigated the effects of fetal ASD exposure on reproduction in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproduction of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproduction of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Exposure to bisphenol A enhanced lung eosinophilia in adult male mice.

BACKGROUND: Bisphenol A (BPA) is useful in many manufacturing processes and is also found in commonly used consumer products. Previous experimental studies have reported that perinatal exposure to BPA promotes the development of allergic lung inflammation in childhood and even into adulthood. In this study, the effects of BPA on allergic lung inflammation in adults were investigated in murine lungs. METHODS: CD-1 mice were orally administrated with 1 mg of BPA/mouse four times at one-week intervals with or without ovalbumin (OVA). The pathologic changes in the airways, cytological alterations in bronchoalveolar lavage fluid (BALF), levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice. In vitro study using RAW264.7 cells, which are macrophage-like cells derived from BALB/c male mice, was conducted. The gene expression of cytokines and chemokines were measured. RESULTS: BPA enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. BPA increased Th2 cytokines-interleukin-13 (IL-13), eosinophil-relevant cytokines and chemokines, such as IL-5, and CCL2 induced by OVA, in BALF. BPA induced adjuvant effects on OVA-specific IgG1 production. In the in vitro study using RAW264.7 cells, BPA increased the mRNA expression of IL-1ß, IL-6, CCL2 and CCL3 compared with the control and OVA groups. CONCLUSIONS: These results suggest that (1) the exposure of BPA could synergize with an OVA challenge to aggravate the severity of lung eosinophilia in adult mice, possibly by promoting a Th2-biased immune response and (2) the activation of macrophages and inflammatory cytokines released from these cells by BPA could be participating in this phenomenon.

Differences in allergic inflammatory responses between urban PM2.5 and fine particle derived from desert-dust in murine lungs.

The biological and chemical natures of materials adsorbed onto fine particulate matter (PM2.5) vary by origin and passage routes. The exacerbating effects of the two samples-urban PM2.5 (U-PM2.5) collected during the hazy weather in a Chinese city and fine particles (ASD-PM2.5) collected during Asian sand dust (ASD) storm event days in Japan-on murine lung eosinophilia were compared to clarify the role of toxic materials in PM2.5. The amounts of ß-glucan and mineral components were higher in ASD-PM2.5 than in U-PM2.5. On the other hand, organic chemicals, including polycyclic aromatic hydrocarbons (PAHs), were higher in U-PM2.5 than in ASD-PM2.5. When BALB/c mice were intratracheally instilled with U-PM2.5 and ASD-PM2.5 (total 0.4 mg/mouse) with or without ovalbumin (OVA), various biological effects were observed, including enhancement of eosinophil recruitment induced by OVA in the submucosa of the airway, goblet cell proliferation in the bronchial epithelium, synergic increase of OVA-induced eosinophil-relevant cytokines and a chemokine in bronchoalveolar lavage fluid, and increase of serum OVA-specific IgG1 and IgE. Data demonstrate that U-PM2.5 and ASD-PM2.5 induced allergic inflammatory changes and caused lung pathology. U-PM2.5 and ASD-PM2.5 increased F4/80(+) CD11b(+) cells, indicating that an influx of inflammatory and exudative macrophages in lung tissue had occurred. The ratio of CD206 positive F4/80(+) CD11b(+) cells (M2 macrophages) in lung tissue was higher in the OVA+ASD-PM2.5 treated mice than in the OVA+U-PM2.5 treated mice. These results suggest that the lung eosinophilia exacerbated by both PM2.5 is due to activation of a Th2-associated immune response along with induced M2 macrophages and the exacerbating effect is greater in microbial element (ß-glucan)-rich ASD-PM2.5 than in organic chemical-rich U-PM2.5.

Desert dust induces TLR signaling to trigger Th2-dominant lung allergic inflammation via a MyD88-dependent signaling pathway.

Asian sand dust (ASD) is known to exacerbate asthma, although its mechanism is not yet well understood. In this study, when the effects on inflammatory response by LPS present in ASD was investigated by measuring the gene expression of cytokines and chemokines in RAW264.7 cells treated with ASD and/or polymyxin B (PMB), the ASD effects were attenuated by PMB, but not completely. When an in vitro study was performed using bone marrow-derived macrophages (BMDMs) from WT, TLR2(-/-), TLR4(-/-), and MyD88(-/-) BALB/c mice and BMDMs from WT, TLR2(-/-), TLR4(-/-), TLR2/4(-/-), TLR7/9(-/-), and MyD88(-/-) C57BL/6J mice, cytokine (IL-6, IL-12) production in BMDMs was higher in ASD-stimulated TLR2(-/-) cells than in TLR4(-/-) cells, whereas it was lower or undetectable in TLR2/4(-/-) and MyD88(-/-) cells. These results suggest that ASD causes cytokine production predominantly in a TLR4/MyD88-dependent pathway. When WT and TLRs 2(-/-), 4(-/-), and MyD88(-/-) BALB/c mice were intratracheally challenged with OVA and/or ASD, ASD caused exacerbation of lung eosinophilia along with Th2 cytokine and eosinophil-relevant chemokine production. Serum OVA-specific IgE and IgG1 similar to WT was observed in TLRs 2(-/-), 4(-/-) mice, but not in MyD88(-/-) mice. The Th2 responses in TLR2(-/-) mice were attenuated remarkably by PMB. These results indicate that ASD exacerbates lung eosinophilia in a MyD88-dependent pathway. TLRs 2 and 4 signaling may be important in the increase in lung eosinophilia. Also, the TLR4 ligand LPS and TLR2 ligand like ß-glucan may be strong candidates for exacerbation of lung eosinophilia.

Silica-carrying particulate matter enhances Bjerkandera adusta-induced murine lung eosinophilia.

Bjerkandera adusta (B. adusta) causes fungus-associated chronic cough. However, the inflammatory response is not yet fully understood. Recently, B. adusta was identified in Asian sand dust (ASD) aerosol. This study investigated the enhancing effects of ASD on B. adusta-induced lung inflammation. B. adusta was inactivated by formalin. ASD was heated to remove toxic organic substances. ICR mice were intratracheally instilled with saline, B. adusta 0.2 µg, or B. adusta 0.8 µg with or without heated ASD 0.1 mg (H-ASD), four times at 2-week intervals. Two in vitro experiments were conducted to investigate any enhancing effects using bone marrow-derived macrophages (BMDM) from Toll-like receptor (TLR) knockout mice and ICR mice. Co-exposure to H-ASD and B. adusta, especially at high doses, caused eosinophil infiltration, proliferation of goblet cells in the airway, and fibrous thickening of the subepithelial layer, and remarkable increases in expression of Th2 cytokines and eosinophil-related cytokine and chemokine expression in bronchoalveolar lavage fluid. In the in vitro study using BMDM from wild-type, TLR2-/-, and TLR4-/- mice, the TLR-signaling pathway for cytokine production caused by B. adusta was predominantly TLR2 rather than TLR4. H-ASD increased the expression of NF-κB and cytokine production by B. adusta in BMDM from ICR mice. The results suggest that co-exposure to H-ASD and B. adusta caused aggravated lung eosinophilia via remarkable increases of pro-inflammatory mediators. The aggravation of inflammation may be related, at least in part, to the activation of the TLR2-NF-κB signaling pathway in antigen presenting cells by H-ASD.

The Role of Toll-Like Receptors and Myeloid Differentiation Factor 88 in Bjerkandera adusta-Induced Lung Inflammation.

BACKGROUND: Recently, a cluster of patients with an intractable allergic fungal cough who were characterized by sensitization to Bjerkandera adusta was reported. In the present study, the role of Toll-like receptors and myeloid differentiation factor 88 (MyD88) in B. adusta-induced lung inflammation was investigated. METHODS: Wild-type (WT), TLR2-/-,TLR4-/-, and MyD88-/- BALB/c mice were intratracheally challenged with B. adusta 4 times at 2-week intervals. Lung pathology, bronchoalveolar lavage fluid (BALF) cytological profiles, and inflammatory mediators in BALF were investigated. Bone marrow-derived macrophages (BMDM) from TLR2-/-,TLR4-/-, TLR2/4-/-, TLR7/9-/-,MyD88-/-, and WT C57BL/6J mice were stimulated with B. adusta for 12 h, and inflammatory mediators in the culture medium were measured. RESULTS: B. adusta caused lung inflammation along with Th2 cytokine [interleukin (IL)-5 and IL-13] and eosinophil-related chemokine [eotaxin and monocyte chemotactic protein (MCP-3)] production, an increase in eosinophils in BALF, and eosinophil infiltration in the airways in WT and TLR4-/- mice. However, Th2 and eosinophil-related responses in TLR2-/- and MyD88-/- mice were low or undetectable. The induction of neutrophils and IL-6, IL-12, IL-17A, and MCP-1 in the BALF of MyD88-/- mice was attenuated compared to that in WT mice. The induction of IL-6, TNF-α, MCP-1, and macrophage inflammatory protein-1α was reduced or undetectable in B. adusta-stimulated BMDM from TLR7/9-/- and MyD88-/- mice compared to WT mice. CONCLUSIONS: These results suggest that TLR2 and the adapter protein MyD88 may play an important role in the induction of eosinophils by B. adusta. However, TLR7/9-MyD88 might be important in the induction of neutrophils and the relevant inflammatory mediators, especially IL-17A.

PM2.5-rich dust collected from the air in Fukuoka, Kyushu, Japan, can exacerbate murine lung eosinophilia.

PM2.5 can exacerbate asthma. Organic substances adsorbed on PM2.5-rich dust (PM2.5rd) were inactivated by heating at 360 °C. To characterize the role of organic substances, the effects of PM2.5rd and heated PM2.5-rich dust (H-PM2.5 rd) on allergic lung inflammation were investigated. BALB/c mice were intratracheally administered PM2.5rd or H-PM2.5rd with or without ovalbumin (OVA) four times at 2-week intervals. PM2.5rd, but not H-PM2.5rd, caused neutrophilic alveolitis and bronchitis. In the presence of OVA, PM2.5rd caused severe eosinophil infiltration and goblet cells proliferation in airways, along with a marked induction of the Th2 cytokines interleukin (IL)-4 and IL-13, and the eosinophil-related cytokine IL-5 in bronchoalveolar lavage fluid (BALF). OVA + H-PM2.5rd caused a weaker response. PM2.5rd showed adjuvant effects on OVA-specific immunoglobulin E (IgE) and IgG1 production, but H-PM2.5rd showed minimal effects. These findings suggested that PM2.5rd-bound substances might aggravate lung eosinophilia. To clarify the roles of TLR2, TLR4, and MyD88 on cytokine production in PM2.5rd, murine bone marrow-derived macrophages (BMDMs) from wild-type (WT), TLR2(-/-), TLR4(-/-), and MyD88(-/-) BALB/c mice were stimulated with dust. Cytokine production was low or undetectable in TLR4(-/-) cells, but occurred from TLR2(-/-) cells, and production by MyD88(-/-) cells was higher than by TLR4(-/-) cells. These results suggest that TLR4 and TLR2 ligands (LPS and ß-glucan, respectively) mainly contributed to cytokines production induced by PM2.5rd. In addition to chemical substances, PM2.5-bound microbial substances might act in inflammatory and allergic lung diseases.

Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas.

Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.

Aggravation of ovalbumin-induced murine asthma by co-exposure to desert-dust and organic chemicals: an animal model study.

BACKGROUND: The organic chemicals present in Asian sand dust (ASD) might contribute to the aggravation of lung eosinophila. Therefore, the aggravating effects of the Tar fraction from ASD on ovalbumin (OVA)-induced lung eosinophilia were investigated. METHODS: The Tar fraction was extracted from ASD collected from the atmosphere in Fukuoka, Japan. ASD collected from the Gobi desert was heated at 360°C to inactivate toxic organic substances (H-ASD). ICR mice were instilled intratracheally with 12 different test samples prepared with Tar (1 µg and 5 µg), H-ASD, and OVA in a normal saline solution containing 0.02% Tween 80. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated. RESULTS: Several kinds of polycyclic aromatic hydrocarbons (PAHs) were detected in the Tar sample. H-ASD + Tar 5 µg induced slight neutrophilic lung inflammation. In the presence of OVA, Tar 5 µg increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 in BALF. Also mild to moderate goblet cell proliferation and mild infiltration of eosinophils in the submucosa of airway were observed. These pathological changes caused by H-ASD + OVA were relatively small. However, in the presence of OVA and H-ASD, Tar, at as low a level as 1 µg, induced severe eosinophil infiltration and proliferation of goblet cells in the airways and significantly increased Th2 cytokines IL-5 and IL-13 in BALF. The mixture showed an adjuvant effect on OVA-specific IgG1 production. CONCLUSIONS: These results indicate that H-ASD with even low levels of Tar exacerbates OVA-induced lung eosinophilia via increases of Th2-mediated cytokines. These results suggest that ASD-bound PAHs might contribute to the aggravation of lung eosinophila.

Enhancement of OVA-induced murine lung eosinophilia by co-exposure to contamination levels of LPS in Asian sand dust and heated dust.

BACKGROUND: A previous study has shown that the aggravation of Asian sand dust (ASD) on ovalbumin (OVA)-induced lung eosinphilia was more severe in lipopolysaccharide (LPS)-rich ASD than in SiO2-rich ASD. Therefore, the effects of different LPS contamination levels in ASD on the aggravation of OVA-induced lung eosinophilia were investigated in the present study. METHODS: Before beginning the in vivo experiment, we investigated whether the ultra-pure LPS would act only on TLR4 or not using bone marrow-derived macrophages (BMDMs) of wild-type, TLR2-/-, TLR4-/- and MyD88-/- BALB/c mice. ASD collected from the desert was heated to remove toxic organic substances (H-ASD). BALB/c mice were instilled intratracheally with 12 different testing samples prepared with LPS (1 ng and 10 ng), H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), the levels of inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated. RESULTS: The LPS exhibited no response to the production of TNF-α and IL-6 in BMDMs from TLR4-/-, but did from TLR2-/-. H-ASD aggravated the LPS-induced neutrophilic lung inflammation. In the presence of OVA, LPS increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 at the levels of 1 ng and 10 ng. In the presence of OVA and H-ASD, LPS induced severe eosinophil infiltration and proliferation of goblet cells in the airways as well as remarkable increases in Th2 cytokines IL-5 and IL-13 in BALF. The mixture containing LPS (1 ng) showed adjuvant activity on OVA-specific IgE and IgG1 production. CONCLUSIONS: The results suggest that H-ASD with naturally-occurring levels of LPS enhances OVA-induced lung eosinophilia via increases in Th2-mediated cytokines and antigen-specific immunoglobulin. These results indicate that LPS is a strong candidate for being a major aggravating substance in ASD.

Lung inflammation by fungus, Bjerkandera adusta isolated from Asian sand dust (ASD) aerosol and enhancement of ovalbumin-induced lung eosinophilia by ASD and the fungus in mice.

BACKGROUND: Bjerkandera adusta (B. adusta) is one of the most important etiological fungi associated with chronic cough. However, precise details of the inflammatory response to exposure are not well understood yet. B. adusta was recently identified in Asian sand dust (ASD) aerosol. Therefore, in the present study the exacerbating effects of ASD on B. adusta-induced lung inflammation and B. adusta + ASD on ovalbumin (OVA)-induced murine lung eosinophilia were investigated using experimental mice. METHODS: In order to prepare testing samples, B. adusta obtained from ASD aerosol was inactivated by formalin and ASD collected from the atmosphere was heated to remove toxic organic substances (H-ASD). CD-1 mice were instilled intratracheally with 12 different samples prepared with various combinations of B. adusta, H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in bronchoalveolar lavage fluid (BALF), and the levels of inflammatory cytokines/chemokines in BALF were investigated. RESULTS: H-ASD aggravated the lung eosinophilia induced by B. adusta alone, which also aggravated the lung eosinophilia induced by OVA. The mixture of OVA, H-ASD, and B. adusta caused serious fibrous thickening of the subepithelial layer, eosinophil infiltration, and proliferation of goblet cells in the airways along with remarkable increases of IL-13, eotaxin, IL-5, and MCP-3 in BALF. CONCLUSIONS: The results of the present study demonstrated that B. adusta isolated from ASD aerosol induces allergic lung diseases. H-ASD enhanced allergic reactions caused by OVA or B. adusta. A mixture of B. adusta, H-ASD, and OVA caused the most remarkable exacerbation to the allergic airway inflammation via remarkable increases of pro-inflammatory mediators.