OBJECTIVE: To determine the expression of nerve growth factor (NGF), tyrosine kinase receptor A (trkA), and pan-neurotrophin receptor (p75) in the lung tissues in asthmatic rats, and to explore their effects on the airway inflammation. METHODS: Thirty-two SD rats were randomly divided into 4 groups: the control, asthma, NGF and anti-NGF groups. The asthmatic model was established by the inhalation and injection of ovalbumin. The total cell count and differential cell count in the bronchoalveolar lavage fluid (BALF) were performed. The pathologic changes in the lung tissues of the 4 groups was detected by HE staining. The NGF mRNA expression in the lung tissues of the asthma and control groups was determined by reverse transcription-polymerase chain reaction (RT-PCR). The changes of trkA and p75 mRNA expressions in the lung tissues in the 4 groups were also investigated by RT-PCR. RESULTS: Compared with the control group, the BALF total cell, the BALF eosinophils (Eos), and the BALF lymphocytes (Lyms) significantly increased (All P <0. 001) in the asthma group; and the lung tissues of the asthma group had more infiltrating inflammatory cells. Not only the expression of NGF mRNA, but also its receptors trkA and p75 mRNA in the lung tissues were significantly higher in the asthma group than those in the control group (All P < 0.01). Positive correlation was found between the expression of NGF mRNA and the BALF total cell, the BALF Lyms in the asthma group. Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the NGF group significantly increased (All P < 0.01), and the lungs of the NGF group had apparent inflammatory changes. The expre-ssions of p75 and trkA mRNA were enhanced significantly (All P < 0.05). Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the anti-NGF group significantly decreased (All P < 0.001), and the lungs of the anti-NGF group showed alleviative inflammatory changes. The expre-ssions of p75 and trkA mRNA significantly decreased (All P < 0.01). CONCLUSION In lungs of asthmatic rats, the elevated expression of NGF mRNA is closely related to the airway inflammation. NGF can upregulate the expressions of p75 and trkA mRNA in asthmatic rats, and then may promote their role in the airway neuronal inflammation in asthma.
Animals ; Asthma ; chemically induced ; metabolism ; Bronchitis ; metabolism ; Lung ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Ovalbumin ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA ; metabolism ; Receptors, Nerve Growth Factor ; metabolism

OBJECTIVE: To explore the effect of Th1/Th2 cytokines on the expression of nerve growth factor(NGF)in splenic lymphocytes in asthmatic model. METHODS: Four SD rats were sensitized and challenged with ovalbumin to establish an asthmatic model, and the rat splenic lymphocytes were isolated and cultured with ConA. The expressions of NGF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and were observed after the lymphocytes were exogenously added with interferon-gamma(IFN-gamma) or interleukin-4 (IL-4). RESULTS: The lymphocytes of the asthmatic model stimulated by ConA in vitro expressed NGF mRNA in a time-dependent manner. After the lymphocytes had been cultured with IL-4 for 12 h, 24 h, 36 h, and 48 h, 50 microg/L IL-4 upregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly higher than the basal values at the same time(all Ps<0.01). After 0, 10, 50, and 100 microg/L IL-4 had been added for 24 h, IL-4 upregulated the expressions of NGF mRNA in a dose-dependent manner and the NGF mRNA expressions were all significantly higher than the values of the lower dose IL-4(all Ps<0.05). After the lymphocytes had been cultured with 10 mug/L IFN-gamma for 0 h, 12 h, 24 h, 36 h, and 48 h, IFN-gamma downregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly lower than the basal values at the same time(all Ps<0.01). After 0, 1, 10, and 50 microg/L IFN-gamma have been added for 24 h, IFN-gamma downregulated the expressions of NGF mRNA in a dose-dependent manner and all the NGF mRNA expressions were significantly lower than the values of the lower IFN-gamma dose(all Ps<0.05). CONCLUSION In the splenic lymphocytes of asthmatic rats, IL-4, one of the Th2 cytokines, can upregulate the expressions of NGF; IFN-gamma, one of the Th1 cytokines, can downregulate the expressions of NGF both in a time-dependent manner and in a dose-dependent manner. Th1/Th2 cytokine immune imbalance may indirectly induce the airway neurogenic inflammation by regulating the NGF mRNA expression.
Animals ; Asthma ; chemically induced ; immunology ; Cells, Cultured ; Cytokines ; pharmacology ; Gene Expression ; drug effects ; Interferon-gamma ; pharmacology ; Interleukin-4 ; pharmacology ; Lymphocytes ; cytology ; drug effects ; metabolism ; Male ; Nerve Growth Factors ; genetics ; Ovalbumin ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen ; cytology ; immunology ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism