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DNA Cell Biol ; 35(3): 146-55, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26720885

RESUMO

Interleukin (IL)-21 has been intensively studied for use in therapy of autoimmune diseases, cancers, and chronic viruses due to its immunomodulatory properties, especially on CD4(+) and CD8(+) T cells and natural killer (NK) cells. The objective of this study was to produce an optimized form of IL-21 with improved stability. Plasmids encoding the murine IL-21 alone (pIL-21) or IL-21 genetically fused to portions from mouse IgG3 (pIL-21/Ig) were constructed, and the efficiency of expression, protein kinetics, biodisponibility, and function were analyzed. The genetic constructions of pIL-21 and pIL-21/Ig were transfected into HEK 293 cells, and significant levels of functional IL-21 were obtained. The amino acid of murine IL-21 and IgG3 cloned showed 100% identity with correspondent published sequences. At 24 h of incubation, increased levels of IL-21 were detected in the supernatants of pIL-21. At 72 h of culture, the levels of IL-21 in the supernatant of cells transfected with pIL-21/Ig were significantly higher than those secreted by pIL-21-transfected cells. Furthermore, the data showed that our chimeric IL-21/Ig present improved systemic disponibility in BALB/c mice and conserved the intrinsic ability to increase the frequency of CD4(+) T cells, NKT cells, and CD8(+) T cells.


Assuntos
Imunoglobulina G/metabolismo , Engenharia de Proteínas/métodos , Receptores de Interleucina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Feminino , Expressão Gênica , Células HEK293 , Humanos , Imunoglobulina G/genética , Injeções , Células Matadoras Naturais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Estabilidade Proteica , Receptores de Interleucina/administração & dosagem , Receptores de Interleucina/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética
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