Unrestricted agonist activity on murine and human cells of a lipopeptide derived from IFN-gamma.

Abstract:

:We describe the isolation of a synthetic agonist of IFN-gamma (L-mIFN-gamma-CT) active on mouse and human cells. Its biological activity is the result of the ability of the C-terminal extremity of murine IFN-gamma to interact with the intracellular part of IFNgamma-R and the observation that the modification of peptides by a palmitic acid enables their cytoplasmic delivery. L-mIFN-gamma-CT stimulated murine cells exhibited an increase in MHC class II molecules and FcgammaRII/III expression and conferred protection against viral lysis. Unresponsiveness to L-mIFN-gamma-CT of cells recovered from IFNgamma-R alpha-chain knockout mice indicated the involvement of IFNgamma-R in the biological activities observed. Induction of VCAM-1, ICAM-1, and HLA-DR expression on human cells stimulated with L-mIFN-gamma-CT demonstrated an abrogation of species specificity. These results describe the development of a new synthetic agonist of IFN-gamma, which substitutes for the native cytokine in any IFN-gamma responsive cells, by acting intracellularly on IFN-gammaR.

authors

Thiam K,Loing E,Delanoye A,Diesis E,Gras-Masse H,Auriault C,Verwaerde C

doi

10.1006/bbrc.1998.9831

subject

Has Abstract

pub_date

1998-12-30 00:00:00

pages

639-47

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)99831-X

journal_volume

253

pub_type

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