Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma.
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.


CONCLUSIONS
Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-beta(1)-mediated airway remodeling in asthma.
Karagiannidis
Christian
C
Swiss Institute of Allergy and Asthma Research Davos (SIAF), Davos, Switzerland.
Hense
Gabriele
G
Martin
Christian
C
Epstein
Michelle
M
Rückert
Beate
B
Mantel
Pierre-Yves
PY
Menz
Günter
G
Uhlig
Stefan
S
Blaser
Kurt
K
Schmidt-Weber
Carsten B
CB
D028341:Activins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits