Interleukin-13 regulates secretion of the tumor growth factor-{beta} superfamily cytokine activin A in allergic airway inflammation.
Activin A is a member of the TGF-beta superfamily and plays a role in allergic inflammation and asthma pathogenesis. Recent evidence suggests that activin A regulates proinflammatory cytokine production and is regulated by inflammatory mediators. In a murine model of acute allergic airway inflammation, we observed previously that increased activin A concentrations in bronchoalveolar lavage (BAL) fluid coincide with Th2 cytokine production in lung-draining lymph nodes and pronounced mucus metaplasia in bronchial epithelium. We therefore hypothesized that IL-13, the key cytokine for mucus production, regulates activin A secretion into BAL fluid in experimental asthma. IL-13 increased BAL fluid activin A concentrations in naive mice and dose dependently induced activin A secretion from cultured human airway epithelium. A key role for IL-13 in the secretion of activin A into the BAL fluid during allergic airway inflammation was confirmed in IL-13-deficient mice. Eosinophils were not involved in this response because there was no difference in BAL fluid activin A concentrations between wild-type and eosinophil-deficient mice. Our data highlight an important role for IL-13 in the regulation of activin A intraepithelially and in BAL fluid in naive mice and during allergic airway inflammation. Given the immunomodulatory and fibrogenic effects of activin A, our findings suggest an important role for IL-13 regulation of activin A in asthma pathogenesis.
Hardy
Charles L
CL
Department of Immunology, Monash University, Commercial Road, Melbourne, VIC 3004 Australia. charles.hardy@med.monash.edu.au
Lemasurier
Jeanne S
JS
Olsson
Fredrik
F
Dang
Thanh
T
Yao
Jun
J
Yang
Ming
M
Plebanski
Magdalena
M
Phillips
David J
DJ
Mollard
Richard
R
Rolland
Jennifer M
JM
O'Hehir
Robyn E
RE
D029404:Activin Receptors / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D028322:Inhibin-beta Subunits / Q000378:metabolism; D018793:Interleukin-13 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D018793:Interleukin-13; D015848:Interleukin-5; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; C103008:inhibin beta A subunit; D028341:Activins; D010047:Ovalbumin; D028322:Inhibin-beta Subunits; D029404:Activin Receptors