Cyclosporine a inhibits TNF production without decreasing TNF mRNA levels

Daniel G. Remick; Dung T. Nguyen; Mark K. Eskandari; Robert M. Strieter; Steven L. Kunkel

doi:10.1016/0006-291X(89)92634-X

Cyclosporine a inhibits TNF production without decreasing TNF mRNA levels

Daniel G. Remick^*, Dung T. Nguyen, Mark K. Eskandari, Robert M. Strieter, Steven L. Kunkel

^*Corresponding author for this work

Surgery, Vascular Surgery Division

Research output: Contribution to journal › Article › peer-review

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Abstract

The role of cytokines in health and disease has received increasing attention and numberous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-α (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 ug/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10μg/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.

Original language	English (US)
Pages (from-to)	551-555
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	161
Issue number	2
DOIs	https://doi.org/10.1016/0006-291X(89)92634-X
State	Published - Jun 15 1989

ASJC Scopus subject areas

Molecular Biology
Biophysics
Biochemistry
Cell Biology

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title = "Cyclosporine a inhibits TNF production without decreasing TNF mRNA levels",

abstract = "The role of cytokines in health and disease has received increasing attention and numberous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-α (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 ug/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10μg/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.",

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AU - Kunkel, Steven L.

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AB - The role of cytokines in health and disease has received increasing attention and numberous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-α (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 ug/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10μg/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.

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Cyclosporine a inhibits TNF production without decreasing TNF mRNA levels

Abstract

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