In vitro and in vivo bioactivity of single-chain interleukin-12
| Autor: | D L, Foss, M D, Moody, K P, Murphy, C, Pazmany, M J, Zilliox, M P, Murtaugh |
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| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Chemical Phenomena Chemistry Physical Protein Conformation Swine Recombinant Fusion Proteins Receptors Interleukin-12 Administration Oral Receptors Interleukin Lymphocyte Activation Interleukin-12 Immunoglobulin A Protein Structure Tertiary Interferon-gamma Structure-Activity Relationship Jejunum Adjuvants Immunologic Species Specificity Immunoglobulin G Macrophages Alveolar Animals Humans Immunization Intestinal Mucosa Signal Transduction |
| Zdroj: | Scandinavian journal of immunology. 50(6) |
| ISSN: | 0300-9475 |
| Popis: | 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-gamma 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 interkeukin-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. |
| Databáze: | OpenAIRE |
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