Cloning and characterization of rhesus IL-18 binding protein, a natural antagonist to IL-18.

Autor: Yellayi S; Division of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA., Braun S, Domingues HG, Kityatana N, Murali R, Johnson RP, Mansfield K, Westmoreland SV, O'Neil SP
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2010 Sep; Vol. 51 (3), pp. 232-9.
DOI: 10.1016/j.cyto.2010.05.010
Abstrakt: IL-18 is a proinflammatory cytokine that is important for host defense, but is also involved in the pathogenesis of a number of disease processes, ranging from autoimmune disorders to atherosclerosis. IL-18 binding protein (IL-18BP) is a constitutively expressed glycoprotein that specifically neutralizes the effects of IL-18, resulting in decreased production of IFN-gamma and reduction in Th1 immune responses. In this study we cloned and sequenced a full-length cDNA of the rhesus IL-18BP (RhIL-18BP) from the spleen of rhesus macaques (Macaca mulatta) and compared its nucleotide and amino acid sequences to the functional murine and human IL-18BP orthologues. In addition, we fused RhIL-18BP to the Fc portion of human IgG1 to make recombinant RhIL-18BP x Fcgamma1 in order to facilitate its detection by Western blot analysis and determined the approximate molecular weight of RhIL-18BP x Fcgamma1 to be 66 kD. With this fusion protein, we showed that RhIL-18BP was functional and could significantly reduce murine IL-18 and LPS-induced IFN-gamma production by murine splenocytes. Furthermore, we demonstrated the expression of IL-18BP in atherosclerotic lesions in a rhesus model of atherosclerosis, underscoring the need to fully understand the role of this protein as a primary negative regulator of IL-18 in multiple disease processes.
(Copyright 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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