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.
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 TNF-alpha secretion, but may be necessary for IFN-gamma-mediated MHC class II induction and IL-1 beta production in human monocytes, whereas phospholipase A2 may not be required for IFN-gamma activation of PKC in the process.
Li
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Department of Neurology, Veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
Milo
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R
Panitch
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Bever
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CT
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004075:Diglycerides / Q000096:biosynthesis; D006683:HLA-DQ Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology
D016207:Cytokines; D004075:Diglycerides; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D016718:Arachidonic Acid; D016899:Interferon-beta; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011433:Propranolol; D011493:Protein Kinase C