Gelsolin secretion in interleukin-4-treated bronchial epithelia and in asthmatic airways.
BACKGROUND
The airway surface liquid, the thin layer of liquid covering the airways, is essential for mucociliary clearance and as a barrier against microbial and other noxious agents. Proteins secreted into the airway surface liquid by epithelial and nonepithelial cells may be important in innate immunity and to improve the fluidity of mucous secretions.


OBJECTIVE
We aimed to identify proteins specifically secreted into the airway surface liquid by human bronchial epithelial cells, in resting conditions and after treatment with interleukin 4 (IL-4), a cytokine released in asthma.


RESULTS
By using a proteomics approach, we found that one of the most abundant proteins was gelsolin, which breaks down actin filaments. Gelsolin mRNA and protein secretion were increased threefold in the airway surface liquid of epithelia treated with IL-4. These results were confirmed at the functional level by measuring actin depolymerization using a fluorescence assay. Gelsolin protein was also upregulated in the airways of subjects with asthma.


CONCLUSIONS
Our findings indicate that gelsolin is released by epithelial cells into the airways and that its secretion is increased by IL-4 in vitro. In addition, we found that the concentration of both IL-4 and gelsolin were raised in the bronchoalveolar lavage of patients with asthma. These results suggest that gelsolin might improve the fluidity of airway surface liquid in asthma by breaking down filamentous actin that may be released in large amounts by dying cells during inflammation.
Candiano
Giovanni
G
Laboratory of Uremic Physiopathology, Istituto G. Gaslini, Genoa-16148, Italy.
Bruschi
Maurizio
M
Pedemonte
Nicoletta
N
Caci
Emanuela
E
Liberatori
Sabrina
S
Bini
Luca
L
Pellegrini
Carlo
C
Viganò
Mario
M
O'Connor
Brian J
BJ
Lee
Tak H
TH
Galietta
Luis J V
LJ
Zegarra-Moran
Olga
O
D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000378:metabolism*; D018260:Gelsolin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D015847:Interleukin-4 / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
D018260:Gelsolin; D012333:RNA, Messenger; D015847:Interleukin-4