Gamma interferon induced increases in intracellular cathepsin B activity in PMA primed THP-1 cells are blocked by inhibitors of protein kinase C.
Macrophage proteinases including cathepsin B (CB) are implicated in the tissue injury of inflammatory lesions. We have previously shown that interferon-gamma (IFN-gamma) increases intracellular levels of the lysosomal proteinase, CB, in THP-1 cell primed with phorbol 12-myristate 13-acetate (PMA). We have now examined the role of protein kinase C (PKC) in this effect. Following activation with PMA, the intracellular CB activity was significantly increased in the presence of 500 U/ml IFN-gamma. With the addition of protein kinase C (PKC) inhibitors bisindolylmaleimide, staurosporine, H-7, or phloretin a reversal of the effect of IFN-gamma was noted whereas the addition of the cyclic nucleotide-dependent protein kinase inhibitors HA 1004, H-8, H-89, or cAMP-Dependent Protein Kinase (PKA) Inhibitor did not block the effect. Although diacylglycerol (DAG) did not replace PMA in the study. Diacylglycerol Kinase Inhibitor induced a more pronounced augmentation and PKC depletion inhibited the effect. This suggests that a PKC-dependent pathway is involved in the response of CB in PMA primed THP-1 cells to IFN-gamma.
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Research Service, Baltimore VAMC, Maryland, USA.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000187:drug effects*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology; D010693:Phloretin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D002401:Cathepsin B; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D010693:Phloretin