Homoharringtonine inhibits allergic inflammations by regulating
NF-κB-miR-183-5p-BTG1 axis
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.