Abstract
BackgroundSteroid 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.ResultsSRC-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.ConclusionsOur 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.
Highlights
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
Enhanced passive systemic anaphylaxis in SRC-3−/−mice To determine the in vivo role of SRC-3 in allergy, we examined the mast cell dependent, IgE-mediated PSA reaction, an extreme form of allergic response [20], in SRC-3−/− and wild-type mice
Passive systemic anaphylaxis was elicited by injecting of 10 μg anti-DNP IgE intravenously, 24 hrs later, mice were administrated with DNP-human serum albumin (DNP-HSA) antigen by intravenously injection, and core body temperature was monitored at indicated time intervals
Summary
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. Mast cell exerts its effect on various IgE-dependent or IgE-independent immune responses through the release of degranules and cytokines and through cellcell interaction [4]. SRC-3 deficiency results in growth retardation and decrease of reproduction rate [10] Besides that, it plays an important role in many physiological and pathologic events such as cell growth, oncogenesis and differentiation [11,12,13,14]. SRC3 represses the production of proinflammatory cytokines including TNF-α, IL-1β and IL-6 through inhibiting cytokine mRNA translation [17]. These results indicate that SRC-3 can suppress inflammatory response. The function of SRC-3 in allergic response and inflammation remains unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
