FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA

Related Experiment Video

Updated: Sep 28, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

J H Hanke1, L N Nichols, M E Coon

  • 1Molecular Genetics Research Department, Pfizer, Inc., Groton, CT 06340.

Lymphokine and Cytokine Research
|October 1, 1992
PubMed

Insights

FK506 and rapamycin, potent immunosuppressants, affect T cell cytokine gene expression. These drugs inhibit IL-2 and GM-CSF at both transcriptional and mRNA stability levels, impacting immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • FK506 and rapamycin are critical macrolide immunosuppressants.
  • They function by inhibiting T cell activation, a key process in immune responses.

Purpose of the Study:

  • To investigate the transcriptional and posttranscriptional effects of FK506 and rapamycin.
  • To analyze their impact on Interleukin-2 (IL-2), Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and IL-2 Receptor alpha (IL-2R alpha) gene expression.

Main Methods:

  • Utilized Northern blot analyses to assess mRNA levels.
  • Employed promoter-reporter constructs to evaluate gene promoter activity.
  • Examined the stability of specific messenger RNAs (mRNAs).

Main Results:

  • FK506 completely inhibited IL-2 promoter activation and partially inhibited GM-CSF promoter activity.
  • Rapamycin partially inhibited both IL-2 and GM-CSF promoter activity.
  • Both drugs destabilized IL-2 and GM-CSF mRNAs, while IL-2R alpha and GAPDH mRNA stability remained unaffected.

Conclusions:

  • FK506 and rapamycin exert dual control over IL-2 and GM-CSF gene expression.
  • Modulation occurs at both the transcriptional and posttranscriptional (mRNA stability) levels.
  • These findings elucidate the complex mechanisms of these immunosuppressive macrolides.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes11:34

A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes

Published on: April 11, 2025

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...