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

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 languageEnglish (US)
Pages (from-to)551-555
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume161
Issue number2
DOIs
StatePublished - Jun 15 1989

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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