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FASEB J 2006 Nov;20(13):2378-80

N-linked glycosylation of IL-13R{alpha}2 is essential for optimal IL-13 inhibitory activity.

Kioi M, Seetharam S, Puri RK

Puri RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, NIH Bldg 29B,Rm 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20892 USA


A high-affinity receptor for interleukin (IL)-13 (interleukin-13Ralpha 2) is over-expressed in disease-related fibroblasts and neoplastic cells and is involved in cancer, allergic, and inflammatory diseases. The extracellular domain of IL-13Ralpha2 (ECDalpha2) could be cleaved, which serves as a decoy receptor. We have expressed and purified ECDalpha2 in both Escherichia coli (E. coli) and mammalian systems as a soluble fragment and studied its biological activities. Although both products of ECDalpha2 showed IL-13 inhibitory activities, mammalian cell-derived ECDalpha2 appeared to be superior compared with purified protein from E. coli. When expressed in E. coli, ECDalpha2 appeared to be a monomer of 42 but a 60 kDa protein when purified from mammalian cells due to heavy glycosylation. The purified glycosylated ECDalpha2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines. The improved potency of mammalian cell-derived ECDalpha2 was shown over ECDalpha2/Fc fusion protein. The N-linked glycosylation of ECDalpha2 was found to be essential for optimal IL-13 inhibitory activity as deglycosylation by PNGase F showed lower activity. ECDalpha2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECDalpha2 are receptor specific. These results indicate that glycosylated ECDalpha2 can serve as a potent inhibitor of IL-13 in a variety of conditions in which IL-13 is a key mediator, e.g., pulmonary, allergic, fibrotic, and neoplastic diseases.--Kioi, M., Seetharam, S., Puri, R. K. N-linked glycosylation of IL-13Ralpha2 is essential for optimal IL-13 inhibitory activity.

Category: Journal Article
PubMed ID: #17023392
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29