Specific inhibition of interleukin-13 activity by a recombinant human single-chain immunoglobulin domain directed against the IL-13 receptor alpha1 chain.

Abstract:

:Interleukin-13 (IL-13) is a T-cell-derived pleiotropic cytokine of particular medical importance because of its critical role in the development of allergic asthma. The effects of IL-13 on its target cells are mediated through a dimeric transmembrane receptor (IL-13R), which shares the IL-4Ralpha subunit with the IL-4R system, but contains as a specific component the IL-13Ralpha1 chain. We have generated a set of single-chain Fv fragments with specific binding capacity to the extracellular domain of the human IL-13Ralpha1 receptor. Bacteriophage clones displaying receptor-binding antibody domains were selected from both naive and synthetic libraries by repetitive panning on recombinant and cell surface-expressed recombinant IL-13Ralpha1. Their specific reactivity with native human IL-13Ralpha1 expressed on the surface of transfected cells was demonstrated by flow cytometry. One binder that specifically interfered with cell activation by IL-13 was extensively characterized. This scFv inhibited IL-13-driven gene transcription and cell proliferation in test cell lines, as well as IL-13-induced activation of primary human monocytes in a dose-dependent manner, with an IC(50) below 300 nM. This novel reagent thus constitutes a valuable tool for the further elucidation of IL-13 function in disease and offers potential therapeutic perspectives.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Knackmuss S,Krause S,Engel K,Reusch U,Virchow JC,Mueller T,Kraich M,Little M,Luttmann W,Friedrich K

doi

10.1515/BC.2007.036

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

325-30

issue

3

eissn

1431-6730

issn

1437-4315

journal_volume

388

pub_type

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