Truncated Chicken Interleukin-1β with Increased Biologic Activity

Gyorfy, Zsuzsa; Ohnemus, Annette; Kaspers, Bernd; Duda, Erno and Staeheli, Peter (2003): Truncated Chicken Interleukin-1β with Increased Biologic Activity. In: Journal of Interferon & Cytokine Research, Vol. 23, No. 3: pp. 223-228

Abstract

Chicken interleukin-1β (ChIL-1β) is synthesized as a precursor molecule that unlike its mammalian counterpart, lacks a typical caspase-1 cleavage site. Therefore, it was unclear if proteolytic cleavage of ChIL-1β can occur and if cleavage might modulate the biologic activity of this cytokine. Using an avian indicator cell line that carries an NF-κB-regulated luciferase reporter gene, we established a sensitive and highly specific bioassay for ChIL-1β. Experiments with a rabbit antiserum indicated that the NF-κB-stimulating activity in supernatants of lipopolysaccharide (LPS)-treated chicken HD-11 macrophages is largely due to IL-1β and that proteolytic processing of natural and recombinant ChIL-1β is not very efficient. Functional analyses further revealed that cDNAs for either full-length or N-terminally truncated chicken ChIL-1β yielded active cytokine. A truncated molecule that closely resembled putative mature ChIL-1β exhibited more than 100-fold enhanced biologic activity after expression in mammalian cells, indicating that precursor cleavage is indeed of critical importance for maximal activity.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Veterinary Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1557-7465
• Language: English