Guanine and inosine nucleotides/nucleosides suppress murine T cell activation.

Abstract

Damaged tissues and cells release intracellular purine nucleotides, which serve as intercellular signaling factors. We previously showed that exogenously added adenine nucleotide (250 μM ATP) suppressed the activation of murine splenic T lymphocytes. Here, we examined the effects of other purine nucleotides/nucleosides on mouse T cell activation. First, we found that pretreatment of mouse spleen T cells with 250 μM GTP, GDP, GMP, guanosine, ITP, IDP, IMP or inosine significantly reduced the release of stimulus-inducible cytokine IL-2. This suppression of IL-2 release was not caused by induction of cell death. Further studies with GTP, ITP, guanosine and inosine showed that pretreatment with these nucleotides/nucleosides also suppressed release of IL-6. However, these nucleotides/nucleosides did not suppress stimulus-induced phosphorylation of ERK1/2, suggesting that the suppression of the release of inflammatory cytokines does not involve inhibition of ERK1/2 signaling. In contrast to ATP pretreatment at the same concentration, guanine or inosine nucleotides/nucleosides did not attenuate the expression of CD25. Our findings indicate that exogenous guanine or inosine nucleotides/nucleosides can suppress inflammatory cytokine release from T cells, and may be promising candidates for use as supplementary agents in the treatment of T cell-mediated immune diseases.

• Authors: Yuria Shinohara, Mitsutoshi Tsukimoto
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 498 Issue 4 Pg. 764-768 (04 15 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 29524424 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Guanine Nucleotides
• Inosine Nucleotides
• Interleukin-2
• Interleukin-6
• Guanosine
• Inosine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Guanine Nucleotides (pharmacology)
• Guanosine (pharmacology)
• Inosine (pharmacology)
• Inosine Nucleotides (pharmacology)
• Interleukin-2 (antagonists & inhibitors, immunology)
• Interleukin-6 (antagonists & inhibitors, immunology)
• Lymphocyte Activation (drug effects)
• Male
• Mice
• Mice, Inbred BALB C
• T-Lymphocytes (drug effects, immunology)