Modulation of allergic responses by mitochondrial STAT3 inhibitors

T. H. Erlich, I. Sharkia, N. Landolina, M. Assayag, O. Goldberger, N. Berkman, F. Levi-Schaffer, E. Razin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: Recently, we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur-1 and Mitocur-3) modulate the allergic response. Methods: Experiments were performed both in vitro in cultured human/mouse mast cells and with rat basophilic leukemia (RBL) cells and also in vivo in mice. The effect of mitochondrial STAT3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels. Results: Here, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in OXPHOS activity and STAT3 serine 727 phosphorylation. It was also observed in an OVA mouse model of allergic asthma that one of the inhibitors used significantly reduced eosinophilia and neutrophilia compared to the control mice group. Furthermore, it was observed that treatment with this inhibitor resulted in a significant reduction in blood histamine levels in mice after IgE-Ag challenge. Conclusion: The present data strongly suggest that the development of mitochondrial STAT3 inhibitors could serve as a potential treatment for allergy-associated diseases.

Original languageAmerican English
Pages (from-to)2160-2171
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume73
Issue number11
DOIs
StatePublished - Nov 2018

Bibliographical note

Publisher Copyright:
© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Keywords

  • STAT3
  • asthma
  • degranulation
  • mast cells
  • mitochondria

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