Deficiency in steroid receptor coactivator 3 enhances cytokine production in IgE-stimulated mast cells and passive systemic anaphylaxis in mice

Cell & Bioscience

Chundong Yu³  Jianming Xu¹  Pingli Mo³  Sidra Majaz³  Kun Liu³  Qiang Chen³  Wei Wan³  Xiaochun Xia² 

[1] Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA;The First Affiliated Hospital of Xiamen University, Xiamen, China;State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiang-An South Road, Xiamen, Fujian 360112, China

关键词: Passive cutaneous anaphylaxis;    Passive systemic anaphylaxis;    Mast cell;    SRC-3;   

Others  :  790817
DOI  :  10.1186/2045-3701-4-21

 received in 2013-12-30, accepted in 2014-02-27,  发布年份 2014

【 摘 要 】

Background

Steroid receptor coactivator 3 (SRC-3) is a multifunctional protein that plays an important role in malignancy of several cancers and in regulation of bacterial LPS-induced inflammation. However, the involvement of SRC-3 in allergic response remains unclear. Herein we used passive systemic anaphylaxis (PSA) and passive cutaneous anaphylaxis (PCA) mouse models to assess the role of SRC-3 in allergic response.

Results

SRC-3-deficient mice exhibited more severe allergic response as demonstrated by a significant drop in body temperature and a delayed recovery period compared to wild-type mice in PSA mouse model, whereas no significant difference was observed between two kinds of mice in PCA mouse models. Mast cells play a pivotal role in IgE-mediated allergic response. Antigen-induced aggregation of IgE receptor (FcϵRI) on the surface of mast cell activates a cascade of signaling events leading to the degranulation and cytokine production in mast cells. SRC-3-deficient bone marrow derived mast cells (BMMCs) developed normally but secreted more proinflammatory cytokines such as TNF-α and IL-6 than wild-type cells after antigen stimulation, whereas there was no significant difference in degranulation between two kinds of mast cells. Further studies showed that SRC-3 inhibited the activation of nuclear factor NF-κB pathway and MAPKs including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in antigen-stimulated mast cells.

Conclusions

Our data demonstrate that SRC-3 suppresses cytokine production in antigen-stimulated mast cells as well as PSA in mice at least in part through inhibiting NF-κB and MAPK signaling pathways. Therefore, SRC-3 plays a protective role in PSA and it may become a drug target for anaphylactic diseases.

【 授权许可】

   
2014 Xia et al.; licensee BioMed Central Ltd.

【 图 表 】

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