Supplementary Material, Supplemental_Figure_S1 – International Journal of Immunopathology and Pharmacology

<p>Supplementary Material, Supplemental_Figure_S1 for International Journal of Immunopathology and Pharmacology by Eiko Koike, Rie Yanagisawa, Tin-Tin Win-Shwe and Hirohisa Takano in International Journal of Immunopathology and Pharmacology</p

Effects of lactational exposure to low-dose BaP on allergic and non-allergic immune responses in mice offspring

<p>Benzo[a]pyrene (BaP) can induce developmental and reproductive toxicity; however, the full scope of its immunotoxic effects remains unknown. This study aimed to assess effects of lactational exposure to low-dose BaP (comparable to human exposure) on potential allergic\non-allergic immune responses in murine offspring. Lactating C3H/HeJ dams were orally dosed with BaP at 0, 0.25, 5.0, or 100 pmol/animal/week) at post-natal days [PND] 1, 8, and 15. Five-weeks-old pups then received intratracheally ovalbumin (OVA) every 2 weeks for 6 weeks. Following the final exposure, mice were processed to permit analyses of bronchoalveolar lavage (BAL) fluid cell profiles as well as levels of lung inflammatory cytokines and chemokines, serum OVA-specific immunoglobulin, and mediastinal lymph node (MLN) cell activation/proliferation. In OVA-sensitized male offspring, lactational low-dose BaP exposure led to enhanced (albeit not significantly) macrophage, neutrophil, and eosinophil infiltration to, and increased T-helper (T_H)-2 cytokine production in, the lungs. In females, BaP exposure, regardless of dose, led to slightly enhanced lung levels of macrophages and eosinophils, and of inflammatory molecules. Protein levels of interleukin (IL)-33 in the OVA + BaP (middle dose) group, and interferon (IFN)-γ in the OVA + BaP (low dose) group, were higher than that of the OVA (no BaP) group. <i>Ex vivo</i> studies showed lactational exposure to BaP partially induced activation of T-cells and antigen-presenting cells (APCs) in the MLN cells of both male and female offspring, with or without OVA sensitization. Further, IL-4 and IFNγ levels in MLN culture supernatants were elevated even without OVA-re-stimulation in OVA + BaP groups. In conclusion, lactational exposure to low-dose BaP appeared to exert slight effects on later allergic and non-allergic immune responses in offspring by facilitating development of modest T_H2 responses and activating MLN cells. In addition, lactational exposures to BaP might give rise to gender differences in allergic/non-allergic immune responses of offspring.</p

Impact of dietary exposure to low-dose tris(1,3-dichloro-2-propyl)phosphate in allergic asthmatic mice

Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphorus flame retardant that is an alternative to brominated flame retardants. Although TDCIPP can adversely affect human health, information about its effects on immune and allergic responses is scarce. We aimed to investigate the effects of dietary exposure to TDCIPP using less than the human tolerable daily intake (TDI) in allergic asthmatic mice. Male C3H/HeJSlc mice were fed a chow diet containing TDCIPP equivalent to 0.02 μg/kg/day (low; L), 0.2 μg/kg/day (medium; M), or 2 μg/kg/day (high; H) and were intratracheally administered ovalbumin (OVA, 1 μg/animal) every 2 weeks from 5 to 11 weeks of age. In OVA-treated mice, TDCIPP-H exposure tended to enhance pulmonary inflammation compared with vehicle exposure. TDCIPP dose-dependently decreased mRNA level of G protein-coupled estrogen receptor (GPER) in the lungs with or without OVA. OVA + TDCIPP-H treatment tended to increase the total cell number and promoted CD4+ cell activation compared with OVA alone treatment in mediastinal lymph nodes. In splenocytes, an increase in the fraction of Breg cells, but not of total B and T cells, and an increase in IL-5 in cell culture supernatants following OVA re-stimulation in OVA + TDCIPP-H-treated mice was observed compared with OVA-alone-treated mice. Moreover, OVA + TDCIPP-H exposure decreased Gr-1 expression in bone marrow (BM) cells. These results suggested that dietary exposure to TDCIPP at TDI level slightly enhances allergic diseases, such as allergic asthma, via GPER regulation at inflamed sites and secondary lymphoid tissue and BM cell alternations.</p

Results of the <i>t</i>-test in terms of average values for all channels (1 to 42) comparing z scores for oxyHb between MCS patients and controls.

<p>Values are expressed as means (± standard deviations).</p><p>*Significant at <i>p</i><0.05.</p><p>Abbreviations: MO, mandarin orange; Pf, perfume; NO, non-odorant; JC, Japanese cypress; Mt, menthol. Numbers in parentheses in column 1 indicate the order of the 10 repetitions (1 to 10).</p

Effects of styrene monomer on a mouse model of atopic dermatitis

Aim: Styrene monomer (SM) is a basic chemical used as a raw material for polystyrene and unsaturated polyester resins and in the production of synthetic resins, synthetic rubbers, paints, and adhesives. To date, it is unclear whether SM is associated with the aggravation of atopic dermatitis. The aim was to investigate the effects of SM on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. Methods: Male mice were injected intradermally with mite allergen on their right ears. In the presence of an allergen, SM (3.5 or 350 μg/animal/week) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expressions of cytokines and chemokines. Results: Macroscopic and microscopic examinations demonstrated that exposure to SM at a dose of 3.5 μg caused an exacerbation of atopic dermatitis-like skin lesions related to mite allergen. These changes were consistent with the level of histamine in the ear tissue as an overall trend. In contrast, 350-μg SM did not show significant enhancement effects. Conclusion: These results indicate that SM exacerbated atopic dermatitis-like skin lesions at hundred-fold lower levels than the level that causes no observed adverse effects as determined by histologic changes in rodent livers. SM could be at least partly responsible for the recent increase in atopic dermatitis.Impact statementStyrene monomer (SM) is classified as an International Agency for Research on Cancer group 2B carcinogen and includes neurotoxicity and respiratory disorders. However, the effects of SM as a chemical substance on existing allergic pathophysiology have not been elucidated yet. This study demonstrated that SM exacerbated murine atopic dermatitis-like skin lesions at hundred-fold lower levels than the level that causes no observed adverse effects as determined by histologic changes in rodent livers, which was concomitant with the local level of histamine. These data hasten a need for comprehensive research to clarify the chemical pollutants’ effects of doses much lower than NOAEL on vulnerable pathophysiologies such as allergy/atopy. Styrene monomer (SM) is classified as an International Agency for Research on Cancer group 2B carcinogen and includes neurotoxicity and respiratory disorders. However, the effects of SM as a chemical substance on existing allergic pathophysiology have not been elucidated yet. This study demonstrated that SM exacerbated murine atopic dermatitis-like skin lesions at hundred-fold lower levels than the level that causes no observed adverse effects as determined by histologic changes in rodent livers, which was concomitant with the local level of histamine. These data hasten a need for comprehensive research to clarify the chemical pollutants’ effects of doses much lower than NOAEL on vulnerable pathophysiologies such as allergy/atopy.</p

Correlation coefficient (r) between rCBF after the first and second exposures to the odor in terms of z scores for all channels (1 to 42).

<p>Values are expressed as Pearson product-moment correlation coefficients.</p><p>*Significant at <i>p</i><0.05.</p><p>Abbreviations: MO, mandarin orange; Pf, perfume; NO, non-odorant; JC, Japanese cypress; Mt, menthol.</p

Experimental setting and NIRS channel orientation.

<p>Detectors and illuminators are shown as gray circles (1 to 14). Channels are shown as white squares (1 to 42). The international 10–20 standard positions and other positional information are indicated. One holder with 42 NIRS channels was set on the PFC of each patient so that the midpoint of channels 38 and 39 corresponded to the intersection point of the F7, F8 and Fz of the international 10–20 system and channels 35 to 38 and 39 to 42 aligned with F8 and F7, respectively.</p

Ratings of hedonic (A) and irritating (B) odours by MCS patients (<i>n</i> = 12) and controls (<i>n</i> = 11) after the olfactory stimulation.

<p>Abbreviations: MO: mandarin orange, Pf: perfume, NO: non-odorant, JC: Japanese cypress, Mt: menthol. Numbers in parentheses indicate orders of ten repetitions (1 to 10). Statistically significant differences between groups are indicated. ^*<i>p</i><0.05, ^**<i>p</i><0.01.</p

Average <i>t</i> value of each channel comparing z scores for oxyHb between MCS patients (<i>n</i> = 12) and controls (<i>n</i> = 11).

<p>Statistically significant differences between groups are indicated as underlined values. ^*<i>p</i><0.05, ^**<i>p</i><0.01. Significant tendencies are indicated: ⁺<i>p</i><0.10.</p

Topographical maps of average z scores for oxyHb in MCS patients (<i>n</i> = 12) and controls (<i>n</i> = 11).

<p>Abbreviations: MO: mandarin orange, Pf: perfume, NO: non-odorant, JC: Japanese cypress, Mt: menthol. Numbers in parentheses indicate the order of the 10 repetitions (1 to 10).</p