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Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma.
J Allergy Clin Immunol. 2006 Jan; 117(1):111-8.JA

Abstract

BACKGROUND

Allergic asthma typically shows activated, allergen-specific CD4(+) T cells in the early phase and airway remodeling in the late phase of the disease. Although TGF-beta plays a crucial role in airway remodeling, it is only marginally induced in CD4(+) T cells in the early allergen-dependent activation of the immune system.

OBJECTIVE

To elucidate the transition between early- and late-phase events, we investigated the role of activin A, a close family member of TGF-beta.

METHODS

Activin A and TGF-beta(1) levels were measured systemically in the serum and in CD4(+) T cells of asthmatic patients, as well as locally in the lung.

RESULTS

Activin A serum levels were increased in patients with severe asthma compared with levels in patients with moderate asthma and healthy control subjects, whereas all patients showed significantly increased TGF-beta(1) serum levels independent of disease severity. In T cells only patients with moderate asthma showed increased activin A mRNA expression, whereas TGF-beta(1) expression was equal to that seen in healthy subjects. Accordingly, ovalbumin sensitization in a mouse model of allergic asthma could induce activin A mRNA expression, but not TGF-beta(1) expression, in the lung. Immunohistochemistry of mice and human specimens revealed an abundant expression of activin A by infiltrating lymphocytes and structural cells of the lung. Although TGF-beta(1) more potently enhanced proliferation and Smad 2/3-dependent reporter genes in fibroblasts, activin A was capable of inducing TGF-beta(1) and vice versa.

CONCLUSION

Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-beta(1)-mediated airway remodeling in asthma.

Authors+Show Affiliations

Swiss Institute of Allergy and Asthma Research Davos (SIAF), Davos, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16387593

Citation

Karagiannidis, Christian, et al. "Activin a Is an Acute Allergen-responsive Cytokine and Provides a Link to TGF-beta-mediated Airway Remodeling in Asthma." The Journal of Allergy and Clinical Immunology, vol. 117, no. 1, 2006, pp. 111-8.
Karagiannidis C, Hense G, Martin C, et al. Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma. J Allergy Clin Immunol. 2006;117(1):111-8.
Karagiannidis, C., Hense, G., Martin, C., Epstein, M., Rückert, B., Mantel, P. Y., Menz, G., Uhlig, S., Blaser, K., & Schmidt-Weber, C. B. (2006). Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma. The Journal of Allergy and Clinical Immunology, 117(1), 111-8.
Karagiannidis C, et al. Activin a Is an Acute Allergen-responsive Cytokine and Provides a Link to TGF-beta-mediated Airway Remodeling in Asthma. J Allergy Clin Immunol. 2006;117(1):111-8. PubMed PMID: 16387593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma. AU - Karagiannidis,Christian, AU - Hense,Gabriele, AU - Martin,Christian, AU - Epstein,Michelle, AU - Rückert,Beate, AU - Mantel,Pierre-Yves, AU - Menz,Günter, AU - Uhlig,Stefan, AU - Blaser,Kurt, AU - Schmidt-Weber,Carsten B, Y1 - 2005/11/08/ PY - 2005/06/20/received PY - 2005/09/13/revised PY - 2005/09/14/accepted PY - 2006/1/3/pubmed PY - 2006/2/10/medline PY - 2006/1/3/entrez SP - 111 EP - 8 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 117 IS - 1 N2 - BACKGROUND: Allergic asthma typically shows activated, allergen-specific CD4(+) T cells in the early phase and airway remodeling in the late phase of the disease. Although TGF-beta plays a crucial role in airway remodeling, it is only marginally induced in CD4(+) T cells in the early allergen-dependent activation of the immune system. OBJECTIVE: To elucidate the transition between early- and late-phase events, we investigated the role of activin A, a close family member of TGF-beta. METHODS: Activin A and TGF-beta(1) levels were measured systemically in the serum and in CD4(+) T cells of asthmatic patients, as well as locally in the lung. RESULTS: Activin A serum levels were increased in patients with severe asthma compared with levels in patients with moderate asthma and healthy control subjects, whereas all patients showed significantly increased TGF-beta(1) serum levels independent of disease severity. In T cells only patients with moderate asthma showed increased activin A mRNA expression, whereas TGF-beta(1) expression was equal to that seen in healthy subjects. Accordingly, ovalbumin sensitization in a mouse model of allergic asthma could induce activin A mRNA expression, but not TGF-beta(1) expression, in the lung. Immunohistochemistry of mice and human specimens revealed an abundant expression of activin A by infiltrating lymphocytes and structural cells of the lung. Although TGF-beta(1) more potently enhanced proliferation and Smad 2/3-dependent reporter genes in fibroblasts, activin A was capable of inducing TGF-beta(1) and vice versa. CONCLUSION: Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-beta(1)-mediated airway remodeling in asthma. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/16387593/Activin_A_is_an_acute_allergen_responsive_cytokine_and_provides_a_link_to_TGF_beta_mediated_airway_remodeling_in_asthma_ DB - PRIME DP - Unbound Medicine ER -