AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distill...AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION:Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.展开更多
基金Supported by The Fundao de Amparo à Pesquisa do Estado de So Paulo
文摘AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION:Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.
