Abstract
Added to HeLa cells previously exposed to recombinant human interferon (IFN)-γ for 20 h, thyroid hormone [L-thyroxine (T4)] in physiological concentrations potentiates the antiviral action of IFN-γ by more than 100- fold in 4 h. We examined protein kinase activities for their contributions to the mechanism of this posttranslational effect of thyroid hormone. Added concurrently with thyroid hormone, the protein kinase C (PKC) inhibitor CGP- 41251 (5 nM) blocked T4 potentiation of IFN-γ action. Coincubated with CGP- 41251, phorbol 12-myristate 13-acetate (PMA) reversed the effect of the inhibitor on thyroid hormone action. U-73122 (10 nM), a phospholipase C inhibitor, also blocked hormone potentiation. KT-5720 (500 nM), a protein kinase A (PKA) inhibitor, completely inhibited the T4 effect, whereas 8- bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) restored hormone action in the presence of KT-5720. In the absence of T4, 8-BrcAMP and PMA, added together to cells in the 4-h paradigm, fully reproduced hormone potentiation of the antiviral effect of IFN-γ. Incubated individually with IFN-γ- treated cells, the two agonists had no potentiating action. Thyroid hormone apparently must activate both PKA and PKC in the nongenomic pathway of IFN- γ action to enhance antiviral activity in HeLa cells.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 271 |
| Issue number | 4 40-4 |
| Publication status | Published - Oct 1996 |
| Externally published | Yes |
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Keywords
- antiviral action
- protein kinase A
- protein kinase C
- thyroid hormone
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry
- Physiology
- Physiology (medical)
Cite this
Potentiation by thyroxine of interferon-γ-induced antiviral state requires PKA and PKC activities. / Lin, Hung Y.; Thacore, Harshad R.; Davis, Faith B.; Davis, Paul J.
In: American Journal of Physiology - Cell Physiology, Vol. 271, No. 4 40-4, 10.1996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potentiation by thyroxine of interferon-γ-induced antiviral state requires PKA and PKC activities
AU - Lin, Hung Y.
AU - Thacore, Harshad R.
AU - Davis, Faith B.
AU - Davis, Paul J.
PY - 1996/10
Y1 - 1996/10
N2 - Added to HeLa cells previously exposed to recombinant human interferon (IFN)-γ for 20 h, thyroid hormone [L-thyroxine (T4)] in physiological concentrations potentiates the antiviral action of IFN-γ by more than 100- fold in 4 h. We examined protein kinase activities for their contributions to the mechanism of this posttranslational effect of thyroid hormone. Added concurrently with thyroid hormone, the protein kinase C (PKC) inhibitor CGP- 41251 (5 nM) blocked T4 potentiation of IFN-γ action. Coincubated with CGP- 41251, phorbol 12-myristate 13-acetate (PMA) reversed the effect of the inhibitor on thyroid hormone action. U-73122 (10 nM), a phospholipase C inhibitor, also blocked hormone potentiation. KT-5720 (500 nM), a protein kinase A (PKA) inhibitor, completely inhibited the T4 effect, whereas 8- bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) restored hormone action in the presence of KT-5720. In the absence of T4, 8-BrcAMP and PMA, added together to cells in the 4-h paradigm, fully reproduced hormone potentiation of the antiviral effect of IFN-γ. Incubated individually with IFN-γ- treated cells, the two agonists had no potentiating action. Thyroid hormone apparently must activate both PKA and PKC in the nongenomic pathway of IFN- γ action to enhance antiviral activity in HeLa cells.
AB - Added to HeLa cells previously exposed to recombinant human interferon (IFN)-γ for 20 h, thyroid hormone [L-thyroxine (T4)] in physiological concentrations potentiates the antiviral action of IFN-γ by more than 100- fold in 4 h. We examined protein kinase activities for their contributions to the mechanism of this posttranslational effect of thyroid hormone. Added concurrently with thyroid hormone, the protein kinase C (PKC) inhibitor CGP- 41251 (5 nM) blocked T4 potentiation of IFN-γ action. Coincubated with CGP- 41251, phorbol 12-myristate 13-acetate (PMA) reversed the effect of the inhibitor on thyroid hormone action. U-73122 (10 nM), a phospholipase C inhibitor, also blocked hormone potentiation. KT-5720 (500 nM), a protein kinase A (PKA) inhibitor, completely inhibited the T4 effect, whereas 8- bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) restored hormone action in the presence of KT-5720. In the absence of T4, 8-BrcAMP and PMA, added together to cells in the 4-h paradigm, fully reproduced hormone potentiation of the antiviral effect of IFN-γ. Incubated individually with IFN-γ- treated cells, the two agonists had no potentiating action. Thyroid hormone apparently must activate both PKA and PKC in the nongenomic pathway of IFN- γ action to enhance antiviral activity in HeLa cells.
KW - antiviral action
KW - protein kinase A
KW - protein kinase C
KW - thyroid hormone
UR - http://www.scopus.com/inward/record.url?scp=0029859219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029859219&partnerID=8YFLogxK
M3 - Article
C2 - 8897832
AN - SCOPUS:0029859219
VL - 271
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 4 40-4
ER -