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In the present work, we explored how two recently developed mitochondrial <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inhibitors (Mitocur\u20101 and Mitocur\u20103) modulate the allergic response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Experiments were performed both in\u00a0vitro in cultured human\/mouse mast cells and with rat basophilic leukemia (<jats:styled-content style=\"fixed-case\">RBL<\/jats:styled-content>) cells and also in\u00a0vivo in mice. The effect of mitochondrial <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inhibitors had no effect on <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in <jats:styled-content style=\"fixed-case\">OXPHOS<\/jats:styled-content> activity and <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 serine 727 phosphorylation. It was also observed in an <jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content> 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\u2010Ag challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present data strongly suggest that the development of mitochondrial <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inhibitors could serve as a potential treatment for allergy\u2010associated diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13467","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T13:26:10Z","timestamp":1524489970000},"page":"2160-2171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Modulation of allergic responses by mitochondrial STAT3 inhibitors"],"prefix":"10.1111","volume":"73","author":[{"given":"T. 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