Interleukin-31 and oncostatin-M mediate distinct signaling reactions and response patterns in lung epithelial cells.
J Biol Chem
; 282(5): 3014-26, 2007 Feb 02.
Article
em En
| MEDLINE
| ID: mdl-17148439
ABSTRACT
Lung epithelial cells are primary targets of oncostatin M (OSM) and, to a lower degree, of interleukin (IL)-6 and IL-31, all members of the IL-6 cytokine family. The OSM receptor (OSMR) signals through activation of STAT and mitogen-activated protein kinase pathways to induce genes encoding differentiated cell functions, reduce cell-cell interaction, and suppress cell proliferation. IL-31 functions through the heteromeric IL-31 receptor, which shares with OSMR the OSMRbeta subunit, but does not engage gp130, the common subunit of all other IL-6 cytokine receptors. Because the response of epithelial cells to IL-31 is unknown, the action of IL-31 was characterized in the human alveolar epithelial cell line A549 in which the expression of the ligand-binding IL-31Ralpha subunit was increased. IL-31 initiated signaling that differed from other IL-6 cytokines by the particularly strong recruitment of the STAT3, ERK, JNK, and Akt pathways. IL-31 was highly effective in suppressing proliferation by altering expression of cell cycle proteins, including up-regulation of p27(Kip1) and down-regulation of cyclin B1, CDC2, CDK6, MCM4, and retinoblastoma. A single STAT3 recruitment site (Tyr-721) in the cytoplasmic domain of IL-31Ralpha exerts a dominant function in the entire receptor complex and is critical for gene induction, morphological changes, and growth inhibition. The data suggest that inflammatory and immune reactions involving activated T-cells regulate functions of epithelial cells by IL-6 cytokines through receptor-defined signaling reactions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucinas
/
Mucosa Respiratória
/
Oncostatina M
/
Pulmão
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2007
Tipo de documento:
Article