Vitro and in vivo bioactivity of single-chain interleukin-12

Dennis L. Foss, M. D. Moody, K. P. Murphy, C. Pazmany, M. J. Zilliox, Michael P Murtaugh

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Interleukin-12 is a heterodimeric cytokine with potent immunoregulatory properties, making it a potential vaccine adjuvant and an immune response modulator. The study of its function is confounded by its heterodimeric structure. In order to facilitate the study of interleukin-12 in both in vitro and in vivo models, we constructed a single-chain porcine interleukin- 12 gene and expressed the recombinant protein in Pichia pastoris. Single- chain porcine interleukin-12 was bioactive in vitro on both human and porcine cells as measured by its ability to induce proliferation of lymphoblasts and interferon-γ secretion by lymph node cells. In contrast, the p40 subunit of porcine interleukin-12 alone did not induce proliferation or inhibit the activity of the single-chain porcine interleukin-12. The in vivo bioactivity of single-chain porcine interleukin-12 was demonstrated in an oral immunization model where it increased antigen-specific IgA and IgG in jejunal mucus. These results indicate that binding of interleukin-12 to its receptor and transduction of intracellular signals requires both p40 and p35 subunits. The bioactivity of interleukin-12 expressed as a single polypeptide will facilitate its in vivo delivery and study of its structure and function.

Original languageEnglish (US)
Pages (from-to)596-604
Number of pages9
JournalScandinavian Journal of Immunology
Volume50
Issue number6
DOIs
StatePublished - 1999

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