Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling

Fu, Shuilian; Ni, Saihong; Wang, Danni; Fu, Meng; Hong, Tian

doi:10.1016/j.intimp.2019.02.041

Cited by 39 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanistically, T-5224 decreased IgE/Ag-induced expression of EGR1 and IL4 and also blocked MAPK activation in activated MCs. A variety of established medicines, including omeprazole (proton pump inhibitor) [ 7 ], tozasertib [ 52 ], and berberine (adenosine monophosphate-activated protein kinase stimulator) [ 53 ] inhibit MC activation-associated MAPK signaling. Meanwhile, T-5224 did not affect maturation of precursor cells into MCs (Additional file 1 : Figure S5).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis

Wang

Zhang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

Background Activator protein-1 (AP1), a c-Fos–JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses. Methods In vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with β-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease. Results c-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by β-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice. Conclusion IgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis

Wang

Zhang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

show abstract

“…For example, metformin, a widely used anti-diabetic drug [34] that also has anti-cancer effects [35–37], has been shown to inhibit IgE and aryl hydrocarbon receptor-mediated mast cell activation in vitro and in vivo [38]. Additionally, the antidiarrheal medicine berberine, which is widely used for gastrointestinal ailments such as bacterial gastroenteritis and dysentery [39], has been found to suppress mast cell-mediated allergic responses via down-regulation of FcɛRI activation and MAPK signaling [40]. Hence, searching among existing drugs for pharmacotherapies that can be repurposed into novel allergic disease treatments that target mast cell activation represents a promising strategy.…”

Section: Discussionmentioning

confidence: 99%

CDK4/6 inhibitor palbociclib suppresses IgE-mediated mast cell activation

Hou

Sun

et al. 2019

J Transl Med

View full text Add to dashboard Cite

Background Mast cell activation causes degranulation and release of cytokines, thereby promoting inflammation. The aim of this study was to investigate the inhibitory effect of CDK4/6 inhibition on mast cell activation in vitro and in vivo. Methods RBL-2H3 rat basophilic leukemia cells (BLCs) and mouse bone marrow-derived mast cells (BMMCs) were sensitized with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated with DNP-human serum albumin (HSA) antigens, and treated with the CDK4/6 inhibitor palbociclib. Histological stains were applied to reveal cytomorphological changes. Murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models were used to examine palbociclib effects on allergic reactions in vivo. Western blots were performed to detect the expression of cell signaling molecules associated with mast cell activation. Results Activated BLCs and BMMCs released copious granule-related mediators (histamine and β-hexosaminidase), which was reduced by palbociclib in a concentration-dependent manner. Palbociclib inhibited expression of the mast cell activation marker CD63 in activated BLCs and inhibited granule release (visualized with toluidine blue staining) while preventing morphological changes, (elongated shape maintained) and filamentous actin (F-actin) reorganization. Palbociclib suppressed molecular Lyn and/or mitogen-activated protein kinase (MAPK) signaling associated with mast cell activation in stimulated BLCs and attenuated allergic reactions in PCA mice dose dependently. Palbociclib attenuated body temperature reduction and diminished serum histamine levels in ovalbumin OVA-challenged ASA mice. Conclusion Palbociclib suppresses IgE-mediated mast cell activation in vitro and in vivo, suggesting that it may be developed into a therapy for mast cell-mediated allergic diseases via inhibition of mast cell degranulation.

show abstract

“…Mast cells induce allergic inflammation through the secretion of inflammatory mediators [ 1 ], and a variety of cell membrane receptors are expressed on their surface. Among them, the combination of IgE and Fc ε RI and the crosslinking of Fc ε RI and multivalent antigens cause degranulation of mast cells, which in turn leads to the release of a large number of inflammatory mediators, including secreted granules (containing histamine and proteases), cytokines (such as TNF- α and IL-13), growth factors, and chemokines [ 2 ], which potentiate inflammatory immune responses via the secretion of cytokines [ 3 ]. Nrf2 is an important transcription factor in the cap'n'collar family.…”

Section: Introductionmentioning

confidence: 99%

Glaucocalyxin A Attenuates Allergic Responses by Inhibiting Mast Cell Degranulation through p38MAPK/NrF2/HO-1 and HMGB1/TLR4/NF-κB Signaling Pathways

Piao

Jiang

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Glaucocalyxin A (GLA) has various pharmacological effects like antioxidation, immune regulation, and antiatherosclerosis. Here, in this study, the effect and mechanism of GLA on mast cell degranulation were studied. The results of the anti-DNP IgE-mediated passive cutaneous anaphylaxis (PCA) showed that GLA dramatically inhibited PCA in vivo, as evidenced by reduced Evans blue extravasation and decreased ear thickness. In addition, GLA significantly reduced the release of histamine and β-hexosaminidase, calcium influx, cytokine (IL-4, TNF-α, IL-1β, IL-13, and IL-8) production in the RBL-2H3 (rat basophilic leukemia cells), and RPMCs (peritoneal mast cells) in vitro. Moreover, we further investigated the regulatory mechanism of GLA on antigen-induced mast cells by Western blot, which showed that GLA inhibited FcεRI-mediated signal transduction and invalidated the phosphorylation of Syk, Fyn, Lyn, Gab2, and PLC-γ1. In addition, GLA inhibited the recombinant mouse high mobility group protein B1- (HMGB1-) induced mast cell degranulation through limiting nuclear translocation of NF-κBp65. Treatment of mast cells with siRNA-HMGB1 significantly inhibited HMGB1 levels, as well as MyD88 and TLR4, decreased intracellular calcium levels, and suppressed the release of β-hexosaminidase. Meanwhile, GLA increased NrF2 and HO-1 levels by activating p38MAPK phosphorylation. Consequently, these data suggest that GLA regulates the NrF2/HO-1 signaling pathway through p38MAPK phosphorylation and inhibits HMGB1/TLR4/NF-κB signaling pathway to reduce mast cell degranulation and allergic inflammation. Our findings could be used as a promising therapeutic drug against allergic inflammatory disease.

show abstract

Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling

Cited by 39 publications

References 29 publications

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis

CDK4/6 inhibitor palbociclib suppresses IgE-mediated mast cell activation

Glaucocalyxin A Attenuates Allergic Responses by Inhibiting Mast Cell Degranulation through p38MAPK/NrF2/HO-1 and HMGB1/TLR4/NF-κB Signaling Pathways

Contact Info

Product

Resources

About