Regulation of mitogen-stimulated human T-cell proliferation, interleukin-2 production, and interleukin-2 receptor expression by protein kinase C inhibitor, H-7.
Recently published reports suggest that the activation of protein kinase C (PKC) plays an important role in the activation pathway of many cell types. In this study, we examined the role of PKC in human T-cell proliferation, IL-2 production, and IL-2R expression, when cultured with the mitogen PHA, the PKC inhibitor H-7, and H-7 control HA1004. H-7 inhibited the PHA-stimulated [3H]thymidine uptake, IL-2 production, and IL-2R expression in a dose-related manner. Further, we found H-7 inhibited T-cell proliferation, IL-2 production, IL-2 mRNA from PHA plus PMA-stimulated cultures. We also found that H-7 inhibited the early-stage activation of PHA-stimulated cells. The presence of exogenous purified human IL-2 or rIL-4 partly reversed the immunosuppression caused by H-7. In contrast, HA1004 had no effect on cell proliferation, IL-2 production, or IL-2R expression. Our results demonstrate that PKC activation is one major pathway through which T-cells become activated.
Atluru
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Department of Anatomy and Physiology, Kansas State University, Manhattan 66506.
Polam
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Atluru
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Woloschak
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013449:Sulfonamides; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D007376:Interleukin-2; D007546:Isoquinolines; D010835:Phytohemagglutinins; D010879:Piperazines; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D013449:Sulfonamides; D014316:Tritium; D015847:Interleukin-4; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D013936:Thymidine