Effect of propranolol and IFN-beta on the induction of MHC class II expression and cytokine production by IFN-gamma IN THP-1 human monocytic cells

Immunopharmacology and Immunotoxicology
Q LiC T Bever

Abstract

This study was undertaken to investigate the effects of propranolol, IFN-beta, and the protein kinase modulators on IFN-gamma induction of MHC class II antigen expression and cytokine production in THP-1 human monocytic cells. IFN-gamma induced expression of HLA-DR and DQ molecules and secretion of the monokines IL-1 beta and TNF-alpha in THP-1 cells in a time and dose-dependent manner. The effect of INF-gamma on class II HLA antigens was dose-dependently inhibited by IFN-beta. H-7, phloretin, staurosporine as well as GF 109203X are selective enzyme inhibitors of protein kinase C (PKC), down-regulating IFN-gamma induced MHC class II expression and cytokine production. Stimulators of PKC, like PMA, replaced IFN-gamma in the induction of monokines in THP-1 cells, whereas the addition of HA 1004 or arachidonic acid to the culture had no effect on IFN-gamma mediated changes. Blocking of phospholipase D (PLD)-derived diacylglycerol (DAG) formation by propranolol abrogated IFN-gamma increased HLA class II expression and IL-1 beta secretion, but had little effect on IFN-gamma induced TNF-alpha production. These findings appear to suggest that PLD-derived phosphatidate is not the primary source of DAG production in IFN-gamma-induced TN...Continue Reading

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Citations

Nov 9, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·T AshikagaS Aiba
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