TY - JOUR
T1 - Regulation of mitogen-stimulated human T-cell proliferation, interleukin-2 production, and interleukin-2 receptor expression by protein kinase C inhibitor, H-7
AU - Atluru, Durgaprasadarao
AU - Polam, Subhashini
AU - Atluru, Subbayamma
AU - Woloschak, Gayle E.
N1 - Funding Information:
’ This work was supported by a grant from the National Institutes of Health, R29CA46964 to D.A. 2 Part ofthis data was presented at 73rd FASEB Annual Meeting, New Orleans, LA; March 19-23, 1989. ’ Present address: Resident Physician, Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73 190. ’ Abbreviations used: PKC, protein kinase C, IL-2, interleukin-2; IL-2R, interleukin-2 receptor; IL-3, interleukin-3, rlL-4, recombinant interleukin-4; PHA, phy-tohemagglutinin; DAG, Diacylglycerol; H-7, I-[S-lsoquinolinesulfonyl]-2-methylpiperazine dihydrochloride; HA 1004, N-[2quanidinoethyl]-5-isoqui-nolinesulfonamidehydrochloride; k,, inhibition constant; PIP*, phosphotidylinositol 4,5 biphosphate; PGEz, prostaglandin Ez; TPA, 12-O-tetradecanoylphorbol-I3-acetate; PMA, phorbol I2-myristate l3-ace.-tate.
PY - 1990/9
Y1 - 1990/9
N2 - 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, and 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.
AB - 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, and 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.
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U2 - 10.1016/0008-8749(90)90207-8
DO - 10.1016/0008-8749(90)90207-8
M3 - Article
C2 - 2383893
AN - SCOPUS:0025071551
VL - 129
SP - 310
EP - 320
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 2
ER -