Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele.

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Presentation transcript:

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele Hense, MD, Christian Martin, PhD, Michelle Epstein, PhD, Beate Rückert, Pierre-Yves Mantel, MSc, Günter Menz, MD, Stefan Uhlig, PhD, Kurt Blaser, PhD, Carsten B. Schmidt-Weber, PhD Journal of Allergy and Clinical Immunology Volume 117, Issue 1, Pages 111-118 (January 2006) DOI: 10.1016/j.jaci.2005.09.017 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 A, Activin A serum levels are increased in patients with moderate asthma (n = 15) who were not treated with steroids, whereas patients with moderate asthma with inhaled GC treatment (n = 22) and patients with severe asthma (n = 29) did not show increased levels. B, TGF-β1 serum levels are increased in both patients with moderate asthma with (n = 20) and without (n = 15) steroid treatment and in patients with severe asthma (n = 29). The dotted area in Fig 1, A, indicates our detection limit of the activin A ELISA. Statistical significance is indicated by asterisks (∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001). Journal of Allergy and Clinical Immunology 2006 117, 111-118DOI: (10.1016/j.jaci.2005.09.017) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 A, Activin βA mRNA expression, measured by means of real-time PCR, is increased in freshly isolated CD4+ T cells of patients with moderate asthma treated with GCs (n = 20) compared with that seen in patients with moderate asthma without steroid treatment (n = 7), patients with severe asthma (n = 14), or healthy control subjects (n = 6). B, In contrast, TGF-β1 mRNA expression is decreased in CD4+ T cells of patients with moderate asthma without GCs compared with that seen in healthy subjects and patients with severe asthma. Data were normalized to one randomly chosen healthy donor and set as 1. Statistical significance is indicated by asterisks (∗P ≤ .05, ∗∗P ≤ .01). Journal of Allergy and Clinical Immunology 2006 117, 111-118DOI: (10.1016/j.jaci.2005.09.017) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 TGF-β1 (5 ng/mL) induces activin A in a noncancer human lung fibroblast cell line (IMR-90; A). In turn, activin A (25 ng/mL) only weakly induces TGF-β1 in IMR-90 (B) cells. In freshly isolated CD4+ T cells from healthy donors, TGF-β1 could not induce activin A (C), and activin A could not induce TGF-β1 (D). PMA (100 ng/mL) was used as a positive control. Data are representative of 4 independent experiments. Error bars indicate the SD of each experiment. Journal of Allergy and Clinical Immunology 2006 117, 111-118DOI: (10.1016/j.jaci.2005.09.017) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Immunohistologic staining of activin βA. Lung sections of OVA-sensitized mice treated with aerosolized PBS (A) or OVA (B) after 90 days are shown. Quantitative analysis of gene expression by means of real-time PCR of activin βA and TGF-β1 mRNA in total lungs of OVA-sensitized and nonsensitized mice, as indicated, are shown in C and D. The figures represent 3 independent experiments. Statistical significance is indicated by asterisks (∗∗P ≤ .01). Error bars indicate the SD of each experiment. Journal of Allergy and Clinical Immunology 2006 117, 111-118DOI: (10.1016/j.jaci.2005.09.017) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Increased proliferation of the human lung fibroblast cell line IMR-90 in response to activin A (A) or TGF-β1 (B). Decreased inhibition of anti-CD3 (5 μg/mL) induced proliferation of CD4+ T cells from a healthy donor in response to activin A (C) or TGF-β1 (D). The results represent 3 independent experiments. Proliferation was measured by means of tritiated thymidine incorporation for 12 hours. Error bars indicate the SD of each experiment. Statistical significance is indicated by asterisks (∗∗P ≤ .01). Journal of Allergy and Clinical Immunology 2006 117, 111-118DOI: (10.1016/j.jaci.2005.09.017) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions