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Group II innate lymphoid cells and microvascular dysfunction from pulmonary titanium dioxide nanoparticle exposure

Abukabda, Alaeddin Bashir, McBride, Carroll Rolland, Batchelor, Thomas Paul, Goldsmith, William Travis, Bowdridge, Elizabeth Compton, Garner, Krista Lee, Friend, Sherri, Nurkiewicz, Timothy Robert·2018·Particle and Fibre Toxicology

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Fig. 1 Characterization of Nano-TiO2. (a) SEM image and (b) Energy dispersive spectroscopy showing elemental composition of the nano-TiO2 suspension used in this study
Fig. 1 Characterization of Nano-TiO2. (a) SEM image and (b) Energy dispersive spectroscopy showing elemental composition of the nano-TiO2 suspension used in this studyCC BY · PubMed Central
Fig. 2 Nano-TiO2 exposure increases T-Helper type II cytokines 4 h post-exposure. Multiplex cytokine analysis showing concentrations of IL-4 (a), IL-1β (b), TNF-α (c), IL-13 (d) and IL-5 (e). Serum samples were obtained at 0, 1, 2 and 4 h post-exposure via tail-vein puncture (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 2 Nano-TiO2 exposure increases T-Helper type II cytokines 4 h post-exposure. Multiplex cytokine analysis showing concentrations of IL-4 (a), IL-1β (b), TNF-α (c), IL-13 (d) and IL-5 (e). Serum samples were obtained at 0, 1, 2 and 4 h post-exposure via tail-vein puncture (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 3 Nano-TiO2 exposure also increases T-Helper type II cytokines 4 h post-exposure in bronchoalveolar lavage fluid (BALF). Multiplex cytokine analysis showing concentrations of IL-4, IL-5, IL-13 in BALF from exposed and control animals 4 h post-exposure (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 3 Nano-TiO2 exposure also increases T-Helper type II cytokines 4 h post-exposure in bronchoalveolar lavage fluid (BALF). Multiplex cytokine analysis showing concentrations of IL-4, IL-5, IL-13 in BALF from exposed and control animals 4 h post-exposure (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 4 Nano-TiO2 exposure is associated with an increase in pulmonary interleukin-33 levels. Lung sections from control (a) and nano-TiO2 exposed (b) animals obtained 4 h post-exposure were stained for interleukin-33. Fluorescence was achieved by staining tracheal sections with an anti-IL-33-FITC conjugated antibody. Relative fluorescence is shown in (c) tagged antibody (N = 6–7). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 4 Nano-TiO2 exposure is associated with an increase in pulmonary interleukin-33 levels. Lung sections from control (a) and nano-TiO2 exposed (b) animals obtained 4 h post-exposure were stained for interleukin-33. Fluorescence was achieved by staining tracheal sections with an anti-IL-33-FITC conjugated antibody. Relative fluorescence is shown in (c) tagged antibody (N = 6–7). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 5 Pre-treatment of nano-TiO2 – exposed animals with an anti-IL-33 antibody lowers BALF and plasma IL-33. Interleukin-33 levels in (a) BALF and (b) plasma in control, nano-TiO2 exposed groups and in rats pre-treated with an anti-IL-33 antibody. Rats were pre-treated with an anti-IL-33 antibody (1 mg/kg) 30 min prior to exposure. Plasma and BALF IL-33 levels were measured 4 h post-exposure. Statistics were analyzed with two-way ANOVA (P ≤ 0.05). * Sham control group vs. nano-TiO2 exposed groups, Ŧ P < 0.05 Exposed + Anti-IL-33 Antibody vs Exposed
Fig. 5 Pre-treatment of nano-TiO2 – exposed animals with an anti-IL-33 antibody lowers BALF and plasma IL-33. Interleukin-33 levels in (a) BALF and (b) plasma in control, nano-TiO2 exposed groups and in rats pre-treated with an anti-IL-33 antibody. Rats were pre-treated with an anti-IL-33 antibody (1 mg/kg) 30 min prior to exposure. Plasma and BALF IL-33 levels were measured 4 h post-exposure. Statistics were analyzed with two-way ANOVA (P ≤ 0.05). * Sham control group vs. nano-TiO2 exposed groups, Ŧ P < 0.05 Exposed + Anti-IL-33 Antibody vs ExposedCC BY · PubMed Central
Fig. 6 Flow cytometric analysis of lung-resident Group II innate lymphoid cells. Flow cytometry of lung tissue 4 h post-exposure for Group II Innate Lymphoid Cells in (a) control and (b) nano-TiO2 exposed animals (N = 6)
Fig. 6 Flow cytometric analysis of lung-resident Group II innate lymphoid cells. Flow cytometry of lung tissue 4 h post-exposure for Group II Innate Lymphoid Cells in (a) control and (b) nano-TiO2 exposed animals (N = 6)CC BY · PubMed Central
Fig. 7 Nano-TiO2 exposure increases pulmonary ILC2 but not ILC1. Quantification of percentage of total pulmonary cells of (a) ILC1 and (b) ILC2 in control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 7 Nano-TiO2 exposure increases pulmonary ILC2 but not ILC1. Quantification of percentage of total pulmonary cells of (a) ILC1 and (b) ILC2 in control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 8 Nano-TiO2 exposure increases NF-ĸB phosphorylation at Serine-468 in isolated ILC2. Quantification of NF-ĸB phosphorylation at (a) serine-468 and (b) serine 536 in isolated ILC2 from isolated. ILC2 from control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 8 Nano-TiO2 exposure increases NF-ĸB phosphorylation at Serine-468 in isolated ILC2. Quantification of NF-ĸB phosphorylation at (a) serine-468 and (b) serine 536 in isolated ILC2 from isolated. ILC2 from control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 9 Th2 cytokine secretion in isolated ILC2 is increased by nano-TiO2 exposure. Multiplex cytokine analysis showing concentrations of IL-4, IL-5, IL-13 supernatant from isolated ILC2 cultured overnight from control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groups
Fig. 9 Th2 cytokine secretion in isolated ILC2 is increased by nano-TiO2 exposure. Multiplex cytokine analysis showing concentrations of IL-4, IL-5, IL-13 supernatant from isolated ILC2 cultured overnight from control and nano-TiO2 exposed animals (N = 6). Statistics were analyzed with two-way ANOVA (P ≤ 0.05), * Sham control group vs. nano-TiO2 exposed groupsCC BY · PubMed Central
Fig. 10 Endothelium-dependent dilation of radial arterioles is blunted by nano-TiO2 exposure and improved by pre-treatment with an anti-IL-33 antibody. Endothelium-dependent dilation of uterine radial arterioles from control, exposed and anti-IL-33 antibody treated animals was determined using pressure myography (n = 12–18). All vascular assessments were performed 24 h post-exposure. Statistics were analyzed with two-way ANOVA (P ≤ 0.05). * Sham control group vs. nano-TiO2 exposed groups, Ŧ P < 0.05 Exposed + Anti-IL-33 Antibody vs Exposed
Fig. 10 Endothelium-dependent dilation of radial arterioles is blunted by nano-TiO2 exposure and improved by pre-treatment with an anti-IL-33 antibody. Endothelium-dependent dilation of uterine radial arterioles from control, exposed and anti-IL-33 antibody treated animals was determined using pressure myography (n = 12–18). All vascular assessments were performed 24 h post-exposure. Statistics were analyzed with two-way ANOVA (P ≤ 0.05). * Sham control group vs. nano-TiO2 exposed groups, Ŧ P < 0.05 Exposed + Anti-IL-33 Antibody vs ExposedCC BY · PubMed Central

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Metadata

Authors
Abukabda, A. B., McBride, C. R., Batchelor, T. P., Goldsmith, W. T., Bowdridge, E. C., Garner, K. L., Friend, S., & Nurkiewicz, T. R.
Venue
Particle and Fibre Toxicology
Published
2018-11-09
Volume
15
Issue
1
ISSN
1743-8977
Cited by
22
References
1
Language
en
Funders
  • FORTESSA (S10 OD016165)
  • FACSAria (S10 RR020866)
  • National Institute of Environmental Health Sciences (R01-ES015022)
  • National Science Foundation (1003907)

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