Thyroid hormone analogues potentiate the antiviral action of interferon-γ by two mechanisms

H. Y. Lin, H. R. Thacore, F. B. Davis, P. J. Davis

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

L-thyroxine (L-T4) potentiates the antiviral activity of human interferon-γ (IFN-γ) in HeLa cells. We have added thyroid hormone and analogues to cells either 1) for 24 h pretreatment prior to 24 h of IFN-γ (1.0 IU/ml), 2) for 24 h cotreatment with IFN-γ, 3) for 4 h, after 20 h cell incubation with IFN-γ, alone, or 4) for 24 h pretreatment and 24 h cotreatment with IFN-γ. The antiviral effect of IFN-γ was then assayed. L-T4 potentiated the antiviral action of IFN-γ by a reduction in virus yield of more than two logs, the equivalent of a more than 100-fold potentiation of the IFN's antiviral effect. 3,3',5-L-triiodothyronine (L-T3) was as effective as L-T4 when coincubated for 24 h with IFN-γ but was less effective than L-T4 when coincubated for only 4 h. D-T4, D-T3, 3,3',5-triiodothyroacetic acid (triac), tetraiodothyroacetic acid (tetrac), and 3,5-diiodothyronine (T2) were inactive. When preincubated with L-T4 for 24 h prior to IFN-γ treatment, tetrac blocked L-T4 potentiation, but, when coincubated with L-T4 for 4 h after 20 h IFN-γ, tetrac did not inhibit the L-T4 effect. 3,3',5'-L-triiodothyronine (rT3) also potentiated the antiviral action of IFN-γ, but only in the preincubation model. Furthermore, the effects of rT3 preincubation and L-T3 coincubation were additive, resulting in 100-fold potentiation of the IFN-γ effect. When L-T4, L-T3, or rT3, plus cycloheximide (5 μg/ml), was added to cells for 24 h and then removed prior to 24 h IFN-γ exposure, the potentiating effect of the three iodothyronines was completely inhibited. in contrast, IFN-γ potentiation by 4 h of L-T4 or L-T3 coincubation was not inhibited by cycloheximide (25 μg/ml). These studies demonstrate two mechanisms by which thyroid hormone can potentiate IFN-γ's effect: 1) a protein synthesis-dependent mechanism evidenced by enhancement of IFN-γ's antiviral action by L-T4, L-T3, or rT3 preincubation, and inhibition of enhancement by tetrac and cycloheximide, and 2) a protein synthesis-independent (posttranslational) mechanism, not inhibited by tetrac or cycloheximide, demonstrated by 4 h coincubation of L-T4 or L-T3, but not rT3, with IFN-γ. The protein synthesis-dependent pathway is responsive to rT3, a thyroid hormone analogue generally thought to have little effect on protein synthesis. A posttranslational mechanism by which the antiviral action of IFN-γ can be regulated has not previously been described.

Original languageEnglish
Pages (from-to)269-276
Number of pages8
JournalJournal of Cellular Physiology
Volume167
Issue number2
DOIs
Publication statusPublished - May 1996
Externally publishedYes

Fingerprint

Thyroid Hormones
Interferons
Antiviral Agents
Cycloheximide
Reverse Triiodothyronine
Triiodothyronine
Proteins
Thyroxine
Viruses
HeLa Cells
Human Activities

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Thyroid hormone analogues potentiate the antiviral action of interferon-γ by two mechanisms. / Lin, H. Y.; Thacore, H. R.; Davis, F. B.; Davis, P. J.

In: Journal of Cellular Physiology, Vol. 167, No. 2, 05.1996, p. 269-276.

Research output: Contribution to journalArticle

Lin, H. Y. ; Thacore, H. R. ; Davis, F. B. ; Davis, P. J. / Thyroid hormone analogues potentiate the antiviral action of interferon-γ by two mechanisms. In: Journal of Cellular Physiology. 1996 ; Vol. 167, No. 2. pp. 269-276.
@article{3f6e0dd35c4b4261836cae6231f26a22,
title = "Thyroid hormone analogues potentiate the antiviral action of interferon-γ by two mechanisms",
abstract = "L-thyroxine (L-T4) potentiates the antiviral activity of human interferon-γ (IFN-γ) in HeLa cells. We have added thyroid hormone and analogues to cells either 1) for 24 h pretreatment prior to 24 h of IFN-γ (1.0 IU/ml), 2) for 24 h cotreatment with IFN-γ, 3) for 4 h, after 20 h cell incubation with IFN-γ, alone, or 4) for 24 h pretreatment and 24 h cotreatment with IFN-γ. The antiviral effect of IFN-γ was then assayed. L-T4 potentiated the antiviral action of IFN-γ by a reduction in virus yield of more than two logs, the equivalent of a more than 100-fold potentiation of the IFN's antiviral effect. 3,3',5-L-triiodothyronine (L-T3) was as effective as L-T4 when coincubated for 24 h with IFN-γ but was less effective than L-T4 when coincubated for only 4 h. D-T4, D-T3, 3,3',5-triiodothyroacetic acid (triac), tetraiodothyroacetic acid (tetrac), and 3,5-diiodothyronine (T2) were inactive. When preincubated with L-T4 for 24 h prior to IFN-γ treatment, tetrac blocked L-T4 potentiation, but, when coincubated with L-T4 for 4 h after 20 h IFN-γ, tetrac did not inhibit the L-T4 effect. 3,3',5'-L-triiodothyronine (rT3) also potentiated the antiviral action of IFN-γ, but only in the preincubation model. Furthermore, the effects of rT3 preincubation and L-T3 coincubation were additive, resulting in 100-fold potentiation of the IFN-γ effect. When L-T4, L-T3, or rT3, plus cycloheximide (5 μg/ml), was added to cells for 24 h and then removed prior to 24 h IFN-γ exposure, the potentiating effect of the three iodothyronines was completely inhibited. in contrast, IFN-γ potentiation by 4 h of L-T4 or L-T3 coincubation was not inhibited by cycloheximide (25 μg/ml). These studies demonstrate two mechanisms by which thyroid hormone can potentiate IFN-γ's effect: 1) a protein synthesis-dependent mechanism evidenced by enhancement of IFN-γ's antiviral action by L-T4, L-T3, or rT3 preincubation, and inhibition of enhancement by tetrac and cycloheximide, and 2) a protein synthesis-independent (posttranslational) mechanism, not inhibited by tetrac or cycloheximide, demonstrated by 4 h coincubation of L-T4 or L-T3, but not rT3, with IFN-γ. The protein synthesis-dependent pathway is responsive to rT3, a thyroid hormone analogue generally thought to have little effect on protein synthesis. A posttranslational mechanism by which the antiviral action of IFN-γ can be regulated has not previously been described.",
author = "Lin, {H. Y.} and Thacore, {H. R.} and Davis, {F. B.} and Davis, {P. J.}",
year = "1996",
month = "5",
doi = "10.1002/(SICI)1097-4652(199605)167:2<269::AID-JCP10>3.0.CO;2-3",
language = "English",
volume = "167",
pages = "269--276",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Thyroid hormone analogues potentiate the antiviral action of interferon-γ by two mechanisms

AU - Lin, H. Y.

AU - Thacore, H. R.

AU - Davis, F. B.

AU - Davis, P. J.

PY - 1996/5

Y1 - 1996/5

N2 - L-thyroxine (L-T4) potentiates the antiviral activity of human interferon-γ (IFN-γ) in HeLa cells. We have added thyroid hormone and analogues to cells either 1) for 24 h pretreatment prior to 24 h of IFN-γ (1.0 IU/ml), 2) for 24 h cotreatment with IFN-γ, 3) for 4 h, after 20 h cell incubation with IFN-γ, alone, or 4) for 24 h pretreatment and 24 h cotreatment with IFN-γ. The antiviral effect of IFN-γ was then assayed. L-T4 potentiated the antiviral action of IFN-γ by a reduction in virus yield of more than two logs, the equivalent of a more than 100-fold potentiation of the IFN's antiviral effect. 3,3',5-L-triiodothyronine (L-T3) was as effective as L-T4 when coincubated for 24 h with IFN-γ but was less effective than L-T4 when coincubated for only 4 h. D-T4, D-T3, 3,3',5-triiodothyroacetic acid (triac), tetraiodothyroacetic acid (tetrac), and 3,5-diiodothyronine (T2) were inactive. When preincubated with L-T4 for 24 h prior to IFN-γ treatment, tetrac blocked L-T4 potentiation, but, when coincubated with L-T4 for 4 h after 20 h IFN-γ, tetrac did not inhibit the L-T4 effect. 3,3',5'-L-triiodothyronine (rT3) also potentiated the antiviral action of IFN-γ, but only in the preincubation model. Furthermore, the effects of rT3 preincubation and L-T3 coincubation were additive, resulting in 100-fold potentiation of the IFN-γ effect. When L-T4, L-T3, or rT3, plus cycloheximide (5 μg/ml), was added to cells for 24 h and then removed prior to 24 h IFN-γ exposure, the potentiating effect of the three iodothyronines was completely inhibited. in contrast, IFN-γ potentiation by 4 h of L-T4 or L-T3 coincubation was not inhibited by cycloheximide (25 μg/ml). These studies demonstrate two mechanisms by which thyroid hormone can potentiate IFN-γ's effect: 1) a protein synthesis-dependent mechanism evidenced by enhancement of IFN-γ's antiviral action by L-T4, L-T3, or rT3 preincubation, and inhibition of enhancement by tetrac and cycloheximide, and 2) a protein synthesis-independent (posttranslational) mechanism, not inhibited by tetrac or cycloheximide, demonstrated by 4 h coincubation of L-T4 or L-T3, but not rT3, with IFN-γ. The protein synthesis-dependent pathway is responsive to rT3, a thyroid hormone analogue generally thought to have little effect on protein synthesis. A posttranslational mechanism by which the antiviral action of IFN-γ can be regulated has not previously been described.

AB - L-thyroxine (L-T4) potentiates the antiviral activity of human interferon-γ (IFN-γ) in HeLa cells. We have added thyroid hormone and analogues to cells either 1) for 24 h pretreatment prior to 24 h of IFN-γ (1.0 IU/ml), 2) for 24 h cotreatment with IFN-γ, 3) for 4 h, after 20 h cell incubation with IFN-γ, alone, or 4) for 24 h pretreatment and 24 h cotreatment with IFN-γ. The antiviral effect of IFN-γ was then assayed. L-T4 potentiated the antiviral action of IFN-γ by a reduction in virus yield of more than two logs, the equivalent of a more than 100-fold potentiation of the IFN's antiviral effect. 3,3',5-L-triiodothyronine (L-T3) was as effective as L-T4 when coincubated for 24 h with IFN-γ but was less effective than L-T4 when coincubated for only 4 h. D-T4, D-T3, 3,3',5-triiodothyroacetic acid (triac), tetraiodothyroacetic acid (tetrac), and 3,5-diiodothyronine (T2) were inactive. When preincubated with L-T4 for 24 h prior to IFN-γ treatment, tetrac blocked L-T4 potentiation, but, when coincubated with L-T4 for 4 h after 20 h IFN-γ, tetrac did not inhibit the L-T4 effect. 3,3',5'-L-triiodothyronine (rT3) also potentiated the antiviral action of IFN-γ, but only in the preincubation model. Furthermore, the effects of rT3 preincubation and L-T3 coincubation were additive, resulting in 100-fold potentiation of the IFN-γ effect. When L-T4, L-T3, or rT3, plus cycloheximide (5 μg/ml), was added to cells for 24 h and then removed prior to 24 h IFN-γ exposure, the potentiating effect of the three iodothyronines was completely inhibited. in contrast, IFN-γ potentiation by 4 h of L-T4 or L-T3 coincubation was not inhibited by cycloheximide (25 μg/ml). These studies demonstrate two mechanisms by which thyroid hormone can potentiate IFN-γ's effect: 1) a protein synthesis-dependent mechanism evidenced by enhancement of IFN-γ's antiviral action by L-T4, L-T3, or rT3 preincubation, and inhibition of enhancement by tetrac and cycloheximide, and 2) a protein synthesis-independent (posttranslational) mechanism, not inhibited by tetrac or cycloheximide, demonstrated by 4 h coincubation of L-T4 or L-T3, but not rT3, with IFN-γ. The protein synthesis-dependent pathway is responsive to rT3, a thyroid hormone analogue generally thought to have little effect on protein synthesis. A posttranslational mechanism by which the antiviral action of IFN-γ can be regulated has not previously been described.

UR - http://www.scopus.com/inward/record.url?scp=0029869328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029869328&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4652(199605)167:2<269::AID-JCP10>3.0.CO;2-3

DO - 10.1002/(SICI)1097-4652(199605)167:2<269::AID-JCP10>3.0.CO;2-3

M3 - Article

C2 - 8613467

AN - SCOPUS:0029869328

VL - 167

SP - 269

EP - 276

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -