Michitaka Tanaka

Dietary supplementation with fructooligosaccharides attenuates allergic peritonitis in mice.

Fructooligosaccharides (FOS) are a prebiotic supplement, which can enhance immunological responses in the host to activate mucosal immunity probably through regulation of gastrointestinal microflora. Nonetheless, the therapeutic potential of prebiotics on allergic pathologies has not been fully elucidated. Therefore, the purpose of this study was to evaluate the preventive and therapeutic effects of dietary supplementation with FOS on a murine model of allergic peritonitis induced by ovalbumin (OVA). Male C3H/HeN mice were intraperitoneally administrated with OVA (1 μg) bi-weekly (Day 0-42, total four times) and were fed a diet containing 0 or 2.5% FOS ad libitum (Day 7-43). At Day 43, mice were killed and several parameters were evaluated. As results, supplementation with FOS alleviated OVA-related peritoneal inflammation characterized by trafficking of polymorphonuclear leukocytes such as eosinophils and neutrophils in the peritoneal cavity. Also, FOS significantly suppressed the protein level of interleukin (IL)-5 and eotaxin in the peritoneal lavage fluid elicited by OVA. In addition, a FOS-supplemented diet significantly reduced the serum allergen specific-IgG(1) level, whereas it significantly increased total IgA levels in the cecal contents as compared with a control diet in the presence of OVA. These results suggest that dietary supplementation with FOS can prevent/ameliorate allergic peritoneal inflammation induced by OVA. The efficacy can at least partially be associated with the regulation of Ig class switching and inhibition of the local expression of IL-5 and eotaxin.

U–Pb age determination for zircons using laser ablation-ICP-mass spectrometry equipped with six multiple-ion counting detectors

Precise zircon U–Pb age determinations have been made on Plesovice zircon using laser ablation-multiple ion counting-inductively coupled plasma-mass spectrometry (LA-MIC-ICP-MS). To achieve high precision and high spatial resolution age determination, multiple ion counting using six electron multipliers was employed. The intensities of Hg–Pb–U isotope (202Hg, 204(Hg + Pb), 206Pb, 207Pb, 208Pb, and 238U) signals were monitored simultaneously without mass scanning. In static acquisition mode, the resultant 238U–206Pb concordia age for Plesovice was 336.3 ± 1.9 Ma, demonstrating improved precision over that achieved using a magnetic sector-based single-collector-ICP-MS, which was 340.3 ± 3.5 Ma for Plesovice. A high duty cycle can be achieved, along with a short integration time or a small sample volume for analysis, allowing high spatial resolution. More importantly, downhole fractionation can be reduced with a shallow ablation pit. To take full advantage of the setup, a one-second LA analysis (8 laser shots with an 8 Hz repetition rate) was adopted for U–Pb age determination. The resultant concordia age for Plesovice was 339.5 ± 6.7 Ma, demonstrating that the repeatability and laboratory bias precision of the resultant age data were comparable to conventional ablation with a single-collector-ICP-MS. The depths and crater diameters of the ablation pits were, respectively, about >1 μm and 25 μm. The data presented herein demonstrate clearly that multiple ion counting-ICP-MS can become a fast and user-friendly tool for use in U–Pb zircon geochronology.

Effects of airway exposure to di-(2-ethylhexyl) phthalate on allergic rhinitis

Abstract Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems.

In vivo immunoamplifying effects of di-(2-ethylhexyl) phthalate on cytokine response

A recent epidemiological study has revealed the positive association between atopy morbidity in children and phthalate esters, environmental chemicals in house dust. Nonetheless, experimental and molecular evidences regarding the correlation between phthalates and allergic response/pathophysiology are not fully investigated. Among phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used for flexible polyvinyl chloride products including vinyl flooring and wall covering. In the present study, we examined the effects of exposure to DEHP on allergen (ovalbumin: OVA) -induced peritonitis in ICR mice. Repeated administration of OVA via intraperitoneal route induced peritoneal inflammation characterized by infiltration of granulocytes (neutrophils and eosinophils) into the cavity. DEHP synergistically exaggerated the OVA-related neutrophilic inflammation. Furthermore, DEHP + OVA profoundly amplified OVA-elicited inflammation- and allergy-related molecules such as interleukin-5, eotaxin, and keratinocyte-derived chemoattractant production/release in the peritoneal cavity. Taken together, DEHP aggravated OVA-related peritoneal inflammation, which is concomitant with local enhanced production/release of inflammation- and allergy-related molecules.

In situ 207Pb/206Pb isotope ratio measurements using two Daly detectors equipped on an ICP-mass spectrometer

The simultaneous detection of 206Pb and 207Pb ions has been made by multiple-ion counting ICP-mass spectrometry using two Daly detectors (MC-ICPMS). To evaluate the long-term gain stability of the detectors, 135Ba/138Ba and 136Ba/138Ba ratios have been measured by a combination of Daly and Faraday detectors (135Ba(D)/138Ba(F)) and an electron multiplier and Faraday detectors (136Ba(EM)/138Ba(F)). The measured 136Ba(EM)/138Ba(F) ratio changed 2% through the 10-hour analysis, whereas the 135Ba(D)/138Ba(F) showed smaller changes (<0.5%) over the 10-hour period, demonstrating that the Daly detector could provide better gain stability against conventional electron multipliers. After the correction for the counting loss due to dead time, the Daly detector is capable of accepting signal intensities as high as 107 cps. This indicates that the overlap of the analysis range, between the Daly detector (100 to 107 cps) and the Faraday detector (104 to 1010 cps), would be at least two orders of magnitude, suggestive of easier cross calibration of the collector gain between the detectors. With the present two Daly detectors, in situ207Pb/206Pb ratio measurements have been made on the Nancy 91500 zircon standard through the sample introduction technique using laser ablation. The overall analytical precision and the relative deviation from the literature values were 5.1% and 0.04%, respectively. The data obtained here clearly demonstrate that the LA-MC-ICPMS technique equipped with the Daly detectors would become a major analytical tool for in situ U–Pb geochronology.

Effects of exposure to nanoparticle-rich diesel exhaust on 8-OHdG synthesis in the mouse asthmatic lung

It has been demonstrated that exposure to diesel exhaust (DE) is associated with the induction and exacerbation of respiratory disorders; however, the impacts of DE containing mainly nanoparticles have been less studied. We have previously demonstrated that inhalation exposure to nanoparticle-rich DE (NR-DE) exacerbated allergic pulmonary inflammation, in the context of enhanced local expression of proinflammatory molecules. However, the underlying mechanisms have not been fully elucidated. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative damage, particularly in DNA. This study examined the effects of NR-DE on 8-OHdG synthesis in the lung in the presence or absence of an allergen. Institute for Cancer Research (ICR) mice were exposed by inhalation to four different gas compositions (control air, low-concentration DE, high-concentration DE and high-concentration DE without particulate matter) for 8 weeks, in the presence or absence of repetitive intratracheal administration of ovalbumin (OVA). Thereafter, we assessed the levels of 8-OHdG synthesis and expression in the lungs by means of enzyme immunoassay (EIA) and immunohistochemistry. The EIA revealed that the level of 8-OHdG was significantly higher in the high-concentration NR-DE-exposed and allergen-sensitized/stimulated group compared with that in the control air-exposed and allergen-treated group. The immunohistochemistry results demonstrated that the level of immunoreactive 8-OHdG was higher in the NR-DE-exposed and allergen-treated lungs compared with that in the corresponding control air-exposed lungs. The results suggested that NR-DE exposure enhanced 8-OHdG formation in asthmatic lungs. This, at least in part, is involved in the NR-DE-mediated exacerbation of the allergic pathophysiology that was identified in our previous study.

In vitro action of sho-seiryu-to on allergen-exposed mononuclear cells.

Although Sho-seiryu-to (SST), used as a traditional herbal (Kampo) medicine mainly in China and Korea, is shown to have immunomodulating potential, such as an anti-allergic one, its underlying mechanism has not been completely clarified. To partially address the issue, we explored its effects on allergen-exposed mononuclear cells. Male balb/c mice were intraperitoneally administered ovalbumin (OVA: 20 μg) plus alum or vehicle twice (Day 0 and Day 14). At Day 21, mice were sacrificed and splenocytes (mononuclear cells) were isolated and cultured in the presence or absence of OVA with or without SST. Thereafter, helper T-related cytokines in the culture supernatants were evaluated by means of ELISA. Protein level of interferon-γ was lower than 5.0 pg/mL in the supernatants from OVA-non-exposed or -exposed mononuclear cells in the presence or absence of OVA stimulation. On the other hand, SST induced the cytokine from both types of mononuclear cells in the presence (P < 0.05) or absence of OVA stimulation as compared to corresponding control. By contrast, interleukin (IL)-4 level tended to be decreased by SST in OVA-non-exposed mononuclear cells as did IL-13 in both non-exposed and exposed mononuclear cells as compared to vehicle. In conclusion, immunoregulating efficacy by SST on allergy-prone subjects may include, at least in part, restoring helper T balance mainly through hyperproduction of IFN-γ against mononuclear cells such as lymphocytes.

Physiological effects of brominated flame retardants on NC/Nga mice

Abstract Purpose: Brominated flame retardants (BFRs) are used as an additive or reactive components in various materials. Regarding their health concerns, their immunotoxicity have not been clarified yet. Materials and methods: In the current study, we examined the effects of systemic exposure to two types of BFRs, DE71 and DE79, on pathophysiologic traits of murine atopic dermatitis (AD). Male NC/Nga mice were repeatedly injected intraperitoneally with DE71 and DE79 and/or mite allergen (Dermatophagoides pteronyssinus: Dp) into their right ears. Thereafter, clinical scores, macroscopic findings of inflammatory foci, and Ig values in serum were examined. Results: Both DEs significantly aggravated clinical scores induced by mite allergen including skin dryness and edema. Total IgE titer was significantly greater in the Dp + DE79 group than in the Dp group. Conclusions: Taken together, exposure to BFRs can exacerbate AD-like skin lesions related to mite allergen in mice. The accentuating effects may be mediated, at least in part, through hyperproduction of IgE.

Ambient fine and coarse particles in Japan affect nasal and bronchial epithelial cells differently and elicit varying immune response

Ambient particulate matter (PM) epidemiologically exacerbates respiratory and immune health, including allergic rhinitis (AR) and bronchial asthma (BA). Although fine and coarse particles can affect respiratory tract, the differences in their effects on the upper and lower respiratory tract and immune system, their underlying mechanism, and the components responsible for the adverse health effects have not been yet completely elucidated. In this study, ambient fine and coarse particles were collected at three different locations in Japan by cyclone technique. Both particles collected at all locations decreased the viability of nasal epithelial cells and antigen presenting cells (APCs), increased the production of IL-6, IL-8, and IL-1β from bronchial epithelial cells and APCs, and induced expression of dendritic and epithelial cell (DEC) 205 on APCs. Differences in inflammatory responses, but not in cytotoxicity, were shown between both particles, and among three locations. Some components such as Ti, Co, Zn, Pb, As, OC (organic carbon) and EC (elemental carbon) showed significant correlations to inflammatory responses or cytotoxicity. These results suggest that ambient fine and coarse particles differently affect nasal and bronchial epithelial cells and immune response, which may depend on particles size diameter, chemical composition and source related particles types.

Ex vivo effects of naphthoquinones on allergen-sensitized mononuclear cells in mice.

Naphthoquinone (NQ), one of the extractable chemical compounds of diesel exhaust particles, enhances allergic asthma traits in mice. However, it remains unknown whether: (1) several types of NQs have the same potential to facilitate allergies; and (2) NQs synergistically disrupt the functional phenotypes of immune cells. The aim of the present study was to investigate the effects of two types (1,2- and 1,4-) of NQs on sensitized mononuclear cells using an ex vivo assay. Male BALB/c mice were repeatedly and intraperitoneally administered ovalbumin (OVA: 20 µg) plus alum with or without two different doses of each NQ. After the final administration, splenocytes (mononuclear cells) were isolated from these mice and cultured in the presence of OVA. Helper T-related cytokines in the culture supernatants and downstream molecules were then evaluated. Protein levels of interferon-γ were higher in the supernatants from 1,2-NQ and 1,4-NQ at low dose + OVA-exposed mononuclear cells following the OVA stimulation than in those from OVA-exposed mononuclear cells. Interleukin (IL)-13 levels were higher in the supernatants from low dose NQs + OVA-exposed mononuclear cells. IL-17 levels were significantly higher in the supernatants from low dose 1,2-NQ + OVA-exposed mononuclear cells. The quantity of phosphorylated STAT6 in the nuclei of these cells was significantly greater in the low dose NQ + OVA groups than in the OVA group. These findings suggest NQs differently enhance allergen sensitization in the context of the Th response against mononuclear cells such as lymphocytes.