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Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma  Kyung S. Lee, MS, Sun M. Jin,

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Presentation on theme: "Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma  Kyung S. Lee, MS, Sun M. Jin,"— Presentation transcript:

1 Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma  Kyung S. Lee, MS, Sun M. Jin, BS, Seung S. Kim, MD, Yong C. Lee, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 113, Issue 5, Pages (May 2004) DOI: /j.jaci

2 Fig 1 Effect of doxycycline, MMPI-I, or MMPI-II on MMP-9 expression in lung tissues and BAL fluids of TDI-sensitized and TDI-challenged mice. Sampling was performed at 72 hours after the TDI challenge in the mice treated with vehicle only (EO), EO plus TDI (ET), EO plus TDI plus DMSO (ETV), EO plus TDI plus doxycycline (ETDo), EO plus TDI plus MMPI-I (ETMI), or EO plus TDI plus MMPI-II (ETMII). A and B, RT-PCR of MMP-9. Densitometric analyses are presented as the relative ratio of MMP-9 mRNA to GAPDH mRNA. The relative ratio of MMP-9 mRNA in the lung tissues of EO mice is arbitrarily presented as 1. C and D, Western blotting of MMP-9. Densitometric analyses are presented as the relative ratio of MMP-9 to actin. The relative ratio of MMP-9 in the lung tissues of EO mice is arbitrarily presented as 1. E and F, Gelatin zymography. Lane S contains standards: the proform of MMP-9 (pMMP-9). Molecular weight markers (open arrowheads on the left) were used to estimate molecular masses. Densitometric analyses are presented as the relative ratio of pMMP-9 levels. The pMMP-9 in the BAL fluids of EO mice (Co) is arbitrarily presented as 1. Data represent the means ± SEMs from 6 independent experiments. ∗P < .05 versus EO. †P < .05 versus EO plus TDI. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

3 Fig 2 Localization of immunoreactive MMP-9 in lung tissues and BAL fluids of TDI-sensitized and TDI-challenged mice. Sampling was performed at 72 hours after the TDI challenge in the mice treated with vehicle only (A and E), EO plus TDI (B and F), EO plus TDI plus doxycycline (C and G), or EO plus TDI plus MMPI-I (D and H). A-D, Representative light microscopy of MMP-9–positive cells in the bronchioles; the brown color indicates MMP-9–positive cells. E-H, Representative light microscopy of MMP-9–positive cells in the BAL fluids; the dark brown color indicates MMP-9–positive cells. Bars indicate scale of 50 (A-D) or 10 (E-H) μm. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

4 Fig 3 Effect of doxycycline, MMPI-I, or MMPI-II on total and differential cellular components of BAL fluids in the TDI-sensitized and TDI-challenged mice. Sampling was performed after treatment with vehicle only (EO), EO plus TDI (ET), EO plus TDI plus DMSO (ETV), EO plus TDI plus doxycycline (ETDo), EO plus TDI plus MMPI-I (ETM I), or EO plus TDI plus MMPI-II (ETM II). Bars represent the means ± SEMs from 6 independent experiments. ∗P < .05 versus EO. †P < .05 versus EO plus TDI. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

5 Fig 4 Effect of doxycycline, MMPI-I, or MMPI-II in lung tissues of TDI-sensitized and TDI-challenged mice. Representative hematoxylin and eosin-stained sections of the lungs. Sampling was performed at 72 hours after the TDI challenge in the mice treated with vehicle only (A), EO plus TDI (B), EO plus TDI plus DMSO (C), EO plus TDI plus doxycycline (D), EO plus TDI plus MMPI-I (E), or EO plus TDI plus MMPI-II (F). Bars indicate scale of 50 μm. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

6 Fig 5 Effect of TDI challenge and doxycycline, MMPI-I, or MMPI-II on airway responsiveness in TDI-sensitized and TDI-challenged mice. Airway responsiveness was measured at 72 hours after the TDI challenge in the mice treated with vehicle only (EO), EO plus TDI (ET), EO plus TDI plus DMSO (ETV), EO plus TDI plus doxycycline (ETDo), EO plus TDI plus MMPI-I (ETM I), or EO plus TDI plus MMPI-II (ETM II). Data represent the means ± SEMs from 6 independent experiments. ∗P < .05 versus EO. †P < .05 versus EO plus TDI. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

7 Fig 6 Effect of doxycycline, MMPI-I, or MMPI-II on p-Akt and Akt protein expression in lung tissues of TDI-sensitized and TDI-challenged mice. p-Akt and Akt protein expression were measured at 72 hours after the TDI challenge in the mice treated with vehicle only (EO), EO plus TDI (ET), EO plus TDI plus DMSO (ETV), EO plus TDI plus doxycycline (ETDo), EO plus TDI plus MMPI-I (ETM I), or EO plus TDI plus MMPI-II (ETM II). Densitometric analyses are presented as the relative ratio of p-Akt to Akt. The relative ratio of p-Akt in the lung tissues of EO mice is arbitrarily presented as 1. Data represent the means ± SEMs from 6 independent experiments. ∗P < .05 versus EO. †P < .05 versus EO plus TDI. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

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