SRC 3 deficiency results in growth retardation and de crease of reproduction ra

SRC 3 deficiency results in growth retardation and de crease of reproduction buy KU-55933 rate. Besides that, it also plays an important role in many physiological and pathologic events such as cell growth, oncogenesis and differentiation. Studies showed that SRC 3 is overexpressed in many tumors, while other studies displayed SRC 3 functions as a tumor suppressor. Therefore, the oncogenic or tumor suppressor effect of SRC 3 depends on the cell context. We have previously demonstrated that SRC 3 mice are highly susceptible to LPS induced le thality and are markedly susceptible to the lethality caused by E. coli induced peritonitis. In addition, SRC 3 represses the production of proinflammatory cytokines including TNF, IL 1B and IL 6 through inhibiting cyto kine mRNA translation.<br><br> These results indicate that SRC 3 can suppress inflammatory response. However, the function of SRC 3 in allergic Linifanib FLT-3 阻害剤 response and inflammation re mains unknown. Anaphylaxis is a severe, systemic allergic reaction in volving the respiratory and cardiovascular systems, usu ally with additional cutaneous and or gastrointestinal features. Traditional treatments for allergic diseases have some limitations such as efficacy deficiency or se vere side effect, thus new targets are being explored for development of new drugs. In this study, we used SRC 3 mice to determine the role of SRC 3 in IgE mediated anaphylaxis. We found that SRC 3 mice suffered severe passive systemic anaphylaxis than wild type mice. In addition, SRC 3 suppressed cytokine pro duction in antigen stimulated mast cells at least in part through inhibiting MAPK and NF κB pathways.<br><br> These results demonstrate that SRC 3 plays a protective role in passive systemic anaphylaxis. Results Enhanced passive systemic anaphylaxis in SRC 3 mice To LY294002 ic50 determine the in vivo role of SRC 3 in allergy, we exam ined the mast cell dependent, IgE mediated PSA reaction, an extreme form of allergic response, in SRC 3 and wild type mice. Passive systemic anaphylaxis was elicited by injecting of 10 ug anti DNP IgE intravenously, 24 hrs later, mice were administrated with DNP human serum albumin antigen by intravenously injection, and then core body temperature was monitored at indicated time in tervals. As shown in Figure 1, the body temperature of mice dropped after DNP HSA injection, and a greater drop was observed in SRC 3 mice compared to wild type mice.<br><br> The recovery of body temperature began at 15 min in wild type mice while this event occurred at 40 min in SRC 3 mice. These results suggest that the allergic reaction is more severe in SRC 3 mice compared to wild type mice in PSA animal model. No significant difference in passive cutaneous anaphylaxis between SRC 3 and wild type mice To further investigate the role of SRC 3 in anaphylaxis, we performed another allergic mouse model named passive cutaneous anaphylaxis. In PCA, local extravasation is induced by local injection of anti DNP IgE and intraven ous injection of DNP HSA. The ears of both wild type and SRC 3 mice were intradermally injected with anti DNP IgE, then DNP HSA and Evans blue dye were injected 24 h later.