| Object:Bronchial asthma is a kind of disease which involves various kinds of cells, cytokines, mediators of inflammation, and airway hyperreactivity is the characteristic of this disease. the causes of the disease are complicated and the pathogens are not very clear now. Nerve growth factor is a kind of multifunctional neurotrophic factor, which can affect the growth, development and survival of the nerve cells. That plays an important role in the inflammatory reaction. The level of NGF is obviously high in the serum and bronchoalveolar lavage fluid of asthmatic patient. IL-1βcan be produced by many stimulated cells and has many biological function, as a kind of pre-inflammatory cytokines plays an important role in regulating immunologic response and inflammatory reaction. IL-1βinvolves in the process of asthma as priming agent of all kinds of cytokines. IL-1βcan stimulate fibroblast and then improve the level of NGF. NGF also improves IL-1βexpression in asthma. SH2-B-Src homology and pleckstrin homology domain-containing protein are made up of 4 isomerides, among which SH2-Bβcombines with phosphorylate TrkA receptor and being the substance of TrkA kinase in nerve cells, which is an important signal molecule on the pathway of NGF/TrkA in the cell. SH2-Bβis necessary for the survival and growth of PC12. SH2-Bβstimulates JAK2 and downstream molecules STATs, these transcription factor also affect the produce of other inflammatory factors. Researches have shown that SH2-Bβtakes part in NGF mediated asthma. It's a question whether SH2-Bβinvolves in the inflammatory reaction in the asthma. This research is based on asthmatic mice, it observes and analyzes SH2-Bβantibody to the affection of IL-1βin lower respiratory tract and visceral sensory afferent system of experimental asthmatic mice, at the same time it tests the changes of the level of IL-1βmRNA, the purpose of which shows the function of the SH2-Bβin asthma in genetic expression level in order to find a new way to cure asthma.Methods:Asthma was induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA). By means Of Immunohisto-chemistry and RT-PCR to investigate the regulatory effect of anti-SH2-Bβon IL-1βimmunoreactivity and IL-1βmRNA .Results :The expression of IL-1βprotein was increased significantly in the lung and visceral sensory afferent system (C7～T5 spinal ganglia and the corresponding posterior horn of the spinal cord) of the asthmatic mice compared with the normal control group(p<0.01), but was decreased in the corresponding portion in anti-SH2-Bβgroup compared with the asthmatic mice(p<0.01).The IL-1βmRNA was increased significantly in the lung ,spinal cord and medulla oblongata of the asthmatic mice compared with the normal control group(p<0.01), but was decreased in the corresponding portion in anti-SH2-Bβgroup compared with the asthmatic mice(p<0.01).Discussion:NGF is a multifunctional neurotrophic factors which affects the growth ,development and survival of nerve cells. TrkA is high affinity receptor of NGF. SH2-Bβcombine with TrkA ,it belongs to adapter protein, which is made up of 4 isomerides,α,β,γ,δ. Among which SH2-Bβplays an important role in the growth of PC12.NGF stimulates TrkA to combine with SH2-Bβ, make SH2-Bβphosphorylation then act on Akt/PKB, PKB stimulats bifurcate transcription factor,make PC12 differentiate and proliferate.Janus kinase family is connecting membrane receptor protein tyrosine kinase, which is non-receptor resistance protein tyrosine kinase superfamily. STATs is singnal transducer and transcription activation molecule in the cytoplasm, which is stimulated by protein tyrosine kinase, it plays an important role in cytokine respond, cell activation, cell division and cell proliferation. JAK and STAT are the important path to interleukin, which is called JAK/STAT pathway. SH2-Bβis in the cytoplysm and cell membrane, that connected tyrosine phosphorylation JAK2 through SH2, greatly activate kinase activity. It believes that SH2-Bβare the potential cytoplasm JAK2 activating agent and increases the cytokine singnal through JAK2/STAT, which plays an important role in the cytokine, hormone, growth factor, regulating cytokinase and phosphorylation.Our recent research has shown that SH2-Bβand NGF have induced overexpression in lung, primary afferent neuron and corresponding spinal segment in asthmatic mice, which shows that SH2-Bβand NGF take part in the asthma process. The expression of SH2-Bβis decreased after NGF blocked. SH2-Bβis an important signal molecule in NGF mediated asthma. This examination has found that SH2-Bβantibody giving from nasal cavity can effectively decrease IL-1βexpression in lower respiratory tract, inflammatory cell in the lung, C7～T5 spinal ganglia and corresponding posterior horn in spinal cord and decrease corresponding mRNA expression in lung, spinal cord, oblongata. These results have not been reported in any documents.Inflammatory cell activation and great cytokine, chemokines and medium are released in the tract in asthma ,they form complicated nets, which involve in characteristic airway inflammatory reaction. IL-1βis a typical inflammatory regulator and initiating agent of regulating inflammation. Some researches have also shown that IL-1βplays an important role not only in attack of asthma ,but also in keeping the asthmatic pathologic state. IgE and IL-1βin serum are related to each other in allergic asthmatic state. Some researches have shown that the level of IL-1βin serum of asthmatic patient during asthmatic attack and catabasis stage are obviously higher than control group; The level of IL-1βmRNA in lung of the asthmatic mice model and IL-1βin alveolar irrigating solution are obviously improved. Someone also found that after taking in IL-1βcan increase heterophil granulocyte infiltration and increase airway hyperreactivity caused by bradykinin, which lead to asthma. All of these have indicated that IL-1βin lower tract take part in asthma. The research has also found that the expression of IL-1βin epithelium of tract and inflammatory cell in lung obviously increase, there are probably two paths as follows:①overexpresstion of NGF in lower respiratory tract during asthma combining with tyrosine kinase A of epithelium of tract or specific receptor of inflammatory cell ,induced IL-1βexpression;②NGF expression up-regulation during asthma, overexpresstion of NGF combining with tyrosine kinase A of sensory nerve ending , retrogress to C7～T5 spinal ganglia, make P substance synthesis increase in spinal ganglia, inflammation stimulates sensory nerve ending to release P substance that act on mast cell etc. and make IL-1βimmune positive expression increase. SH2-Bβantibody utilized in nasal cavity obviously decrease IL-1βmRNA synthesis and protein expression during asthma .Researches have shown that NGF and IL-1βexist in developable nerve system. which indicates they function together. On one hand IL-1βinduced the happening of various kinds of neuropeptide and activate many related signal pathway. Researches have shown that IL-1βin spinal ganglia activate PKC and NF2κB then induced CGRP release to produce neurogenic inflammation. On the other hand NGF can upregulate the IL-1βexpression in asthma. Learned from former researches, we can draw a conclusion that NGF up-regulate the IL-1βexpression through up-regulating the SH2-Bβexpression. It is the reason that NGF up-regulate the IL-1βexpression.Susaki has found that NGF improves expression of FcγR and CR3 in macrophage and improves the phagotrophy ability. It produces more IL-1βthrough macrophage TrkA mediated mitogen-activated protein kinase pathway and involves in abnormal reactive inflammation. After SH2-Bβis blocked by antibody in our experiment, IL-1βexpression in lower tract of asthmatic mice ,inflammatory cell in lung, C7～T5 segment spinal ganglia and corresponding posterior horn in spinal cord and correspongding mRNA expression decrease in lung, spinal cord and oblongata. All this has shown that NGF/TrkA/MAPK pathway plays an important role by regulate SH2-Bβduring taking part in onset of asthma.STATs pathway has some unusual ways which lead to inflammatory cell and epithelium of tract secret many cytokine and chemotatic factor by STATs and plays the role in chronic tract inflammation. JAK/STAT are the important path to cytokine signal transducer, SH2-Bβis a potential JAK2 activator in cytoplasm and increase cytokine signal through JAK2/STAT pathway. We should do further research that SH2-Bβantibody down-regulate the expression of IL-1βif it caused after SH2-Bβblocked and result in downstream signal decrease in pathway.Conclusion:SH2-Bβantibody can decrease effectively IL-1βprotein expression in the lung , C7～T5 segmental spinal ganglia and corresponding posterior horn of spinal cord in asthmatic mice, and lowers IL-1βmRNA expression in spinal cord , oblongata. Blocked the SH2-Bβexpression may become a novel effective way to cure allergic asthma...
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