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J Biol Chem. 2010 May 14;285(20):14955-63. doi: 10.1074/jbc.M109.049163. Epub 2010 Mar 24.

Definition and characterization of an inhibitor for interleukin-31.

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1
Unité Mixte Inserm 564, Bâtiment Monteclair, 4 rue Larrey, 49033 Angers Cedex 09, France.

Abstract

Interleukin-31 (IL-31) is a recently described T cell-derived cytokine, mainly produced by T helper type 2 cells and related to the IL-6 cytokine family according to its structure and receptor. IL-31 is the ligand for a heterodimeric receptor composed of a gp130-like receptor (GPL) associated with the oncostatin M receptor (OSMR). A link between IL-31 and atopic dermatitis was shown by studying the phenotype of IL-31 transgenic mice and IL-31 gene haplotypes in patients suffering from dermatitis. In this study, we generated a potent IL-31 antagonist formed by external portions of OSMR and GPL fused with a linker. This fusion protein, OSMR-L-GPL, consisting of 720 amino acids, counteracted the binding of IL-31 to its membrane receptor complex and the subsequent signaling events involving the STATs and MAPK pathways. Neutralizing effects were found in IL-31-sensitive cell lines, including brain-derived cells and primary cultures of keratinocytes.

PMID:
20335179
PMCID:
PMC2865271
DOI:
10.1074/jbc.M109.049163
[Indexed for MEDLINE]
Free PMC Article
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