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Homoharringtonine inhibits allergic inflammations by regulating NF-κB-miR-183-5p-BTG1 axis
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  • Misun Kim,
  • Hyein Jo,
  • Yoojung Kwon,
  • Youngmi Kim,
  • Hyun Suk Jung,
  • Dooil Jeoung
Misun Kim
Kangwon National University
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Hyein Jo
Kangwon National University
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Yoojung Kwon
Kangwon National University
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Youngmi Kim
Hallym University College of Medicine
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Hyun Suk Jung
Kangwon National University
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Dooil Jeoung
Kangwon National University, College of National Science
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Abstract

BACKGROUND AND PURPOSE: Homoharringtonine (HHT) is a drug for treatment of chronic myeloid leukemia. This study investigated the role of homoharringtonine in allergic inflammations. EXPERIMENTAL APPROACH: Mouse model of atopic dermatitis (AD) induced by DNFB and anaphylaxis employing DNP-HSA were used to examine the role of homoharringtonine in allergic inflammations. We investigated roles of miR-183-5p, regulated by HHT in RBL2H3 cells, in AD and anaphylaxis. KEY RESULTS: HHT exerted negative effects on in vitro allergic inflammation and attenuated clinical symptoms associated with AD. AD increased the expression levels of hallmarks of allergic inflammation and induced features of allergic inflammation in rat basophilic leukemia (RBL2H3) cells. HHT prevented DNFB from increasing the expression of Th1/Th2 cytokines in mouse model of AD. HHT inhibited passive cutaneous anaphylaxis and passive systemic anaphylaxis. MiR-183-5p inhibitor inhibited anaphylaxis and AD. B cell translocation gene 1 (BTG1) was shown to be a direct target of miR-183-5p. BTG1 prevented antigen from inducing molecular features of in vitro allergic inflammation. AD increased the expression of NF-kB, and NF-kB showed binding to the promoter sequences of miR-183-5p. NF-kB and miR-183 formed positive feedback to mediate in vitro allergic inflammation. Curcumin inhibited in vitro allergic inflammation and attenuated AD by regulating the expression levels of miR-183-5p and BTG1. Curcumin and miR-183-5p inhibitor prevented cellular interactions involving mast cells and macrophages in AD. CONCLUSIONS AND IMPLICATIONS: HHT can be developed as anti-allergy drug and NF-κB- miR-183-5p-BTG1 axis can serve as a target for the development of anti-allergy drugs.