Objective To investigate the impacts of cytokines （interleukin-4，IL-4；tumor necrosis factor-α，TNF-α） and medications of bronchial asthma （dexamethasone，aminophylline，salbutamol） on the activity of histamine N-methyltransferase（HMT） in tracheal epithelial cells.Methods BEAS-2B bronchial epithelial cells were cultured and treated with different concentration of TNF-α, IL-4, dexamethasone, salbutamol and aminophylline respectively. The activity of HMT in BEAS-2B cells was determined by high performance liquid chromatography.Results The activity of HMT in tracheal epithelial cells was (50±7) pmol?min-1?mg pro-1.TNF-α and IL-4 lowered the activity of HMT significantly at the concentration equal to or higher than 1 ng/mL and 5 ng/mL respectively，and reached the maximum inhibitory effect at the level of 10 ng/mL.Dexamethasone and aminophylline could ameliorate distinctly the inhibitory effect of TNF-α on the activity of HMT, while salbutamol had no significant inhibitory effect.Conclusions TNF-α and IL-4 exert the lowering effect on the activity of HMT，which would be one important cause of airway hyperreactivity.Glucocorticoids and theophyllines are administered to treat asthma partly due to its relieving mechanism of TNF-α negative effects on HMT.
Citation：
LIU Yi,ZHANG Bo,LI Yaohua,JI Shuguo. Experimental study on the activity regulation of histamine N-methyltransferase in tracheal epithelial cells. Chinese Journal of Respiratory and Critical Care Medicine, 2007, 6(1): 19-22. doi:
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Yamauchi K，Sekizawa K，Suzuli H，et al.Structure and function of human histamine N-methyltransferase：critical enzyme in histamine metabolism in airway.Am J Physiol，1994，267：L342-L349.
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| 2. |
Sekizawa K，Nakazawa H，Ohrui T，et al.Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.Am Rev Respir Dis，1993，147：92-96.
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| 3. |
Nakazawa H，Sekizawa K，Morikawa M，et al.Viral respiratory infection causes airway hyperresponsive and decreases histamine N-methyltransferase activity in guinea pigs.Am J Respir Crit Care Med，1994，29：180-185.
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| 4. |
Hoshi H，Yamauchi K，Sekizawa K，et al.Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.Am J Respir Cell Mol Biol，1996，14：76-83.
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Tamaoki J，Araake M，Chiyotani A，et al.Airway hyperresponsiveness to histamine in mycoplasmal infection：role of histamine N-methyltransferase.Eur J Pharmacol，1998，247：257-260.
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Fukuda H，Yamatodani A，Imamura I，et al.High-performance liquid chromatographic determination of histamine N-methyltransferase activity.J Chromatography，1991，567：459-464.
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Lowry OH，Rosebrough NJ，Farr AL，et al.Protein measurement with the Folin phenol reagent.J Biol Chem，1951，193：265-275.
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Bryce PJ，Mathias CB，Harrison KL，et al.The H1 histamine receptor regulates allergic lung responses.J Clin Invest，2006，116：1624-1632.
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Yan L，Galinsky RE，Bernstein JA，et al.Histamine N-methyltransferase pharmacogenetics：association of a common functional polymorphism with asthma.Pharmacogenetics，2000，10：261-266.
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Wheeler AP，Jesmok G，Brigham KL.Tumor necrosis factor’s effects on lung mechanics，gas exchange，and airway reactivity in sheep.J Appl Physiol，1990，68：2542-2549.
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To Y，Dohi M，Tanaka R，et al.Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma.Lab Invest，2001，81：1385-1396.
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Barnes PJ，Pedersen S.Efficacy and safety of inhaled corticosteroids in asthma.Report of a workshop held in Eze，France，October 1992.Am Rev Respir Dis，1993，148：S1-S26.
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Barnes PJ，Adcock I.Anti-inflammatory actions of steroids：molecular mechanisms.Trends Pharmacol Sci，1993，14：436-441.
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| 15. |
Finnerty JP，Lee C，Willson S，et al.Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects.Eur Respir J，1996，9：1672-1677.
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| 16. |
曾艳，郭华民，刘丹，等.经氨茶碱治疗后哮喘大鼠血TNF-α及肺病理改变.小儿急救医学，1998，5：157-159.
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| 17. |
Tomita K，Chikuni H，Tokuyasu H，et al.Functional assay of NF-κB translocation into nuclei by laser scanning cytometry：inhibitory effect by dexamethasone or theophylline.Naumyn Schmiedebergs Arch Oharmacol，1999，359：249-255.
|
- 1. Yamauchi K，Sekizawa K，Suzuli H，et al.Structure and function of human histamine N-methyltransferase：critical enzyme in histamine metabolism in airway.Am J Physiol，1994，267：L342-L349.
- 2. Sekizawa K，Nakazawa H，Ohrui T，et al.Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.Am Rev Respir Dis，1993，147：92-96.
- 3. Nakazawa H，Sekizawa K，Morikawa M，et al.Viral respiratory infection causes airway hyperresponsive and decreases histamine N-methyltransferase activity in guinea pigs.Am J Respir Crit Care Med，1994，29：180-185.
- 4. Hoshi H，Yamauchi K，Sekizawa K，et al.Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.Am J Respir Cell Mol Biol，1996，14：76-83.
- 5. Tamaoki J，Araake M，Chiyotani A，et al.Airway hyperresponsiveness to histamine in mycoplasmal infection：role of histamine N-methyltransferase.Eur J Pharmacol，1998，247：257-260.
- 6. Fukuda H，Yamatodani A，Imamura I，et al.High-performance liquid chromatographic determination of histamine N-methyltransferase activity.J Chromatography，1991，567：459-464.
- 7. Lowry OH，Rosebrough NJ，Farr AL，et al.Protein measurement with the Folin phenol reagent.J Biol Chem，1951，193：265-275.
- 8. Bryce PJ，Mathias CB，Harrison KL，et al.The H1 histamine receptor regulates allergic lung responses.J Clin Invest，2006，116：1624-1632.
- 9. Yan L，Galinsky RE，Bernstein JA，et al.Histamine N-methyltransferase pharmacogenetics：association of a common functional polymorphism with asthma.Pharmacogenetics，2000，10：261-266.
- 10. 汤葳，陈雪华，张奕，等.支气管上皮细胞IL-6和IL-8的研究.上海第二医科大学学报，2005，25：694-697.
- 11. Wheeler AP，Jesmok G，Brigham KL.Tumor necrosis factor’s effects on lung mechanics，gas exchange，and airway reactivity in sheep.J Appl Physiol，1990，68：2542-2549.
- 12. To Y，Dohi M，Tanaka R，et al.Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma.Lab Invest，2001，81：1385-1396.
- 13. Barnes PJ，Pedersen S.Efficacy and safety of inhaled corticosteroids in asthma.Report of a workshop held in Eze，France，October 1992.Am Rev Respir Dis，1993，148：S1-S26.
- 14. Barnes PJ，Adcock I.Anti-inflammatory actions of steroids：molecular mechanisms.Trends Pharmacol Sci，1993，14：436-441.
- 15. Finnerty JP，Lee C，Willson S，et al.Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects.Eur Respir J，1996，9：1672-1677.
- 16. 曾艳，郭华民，刘丹，等.经氨茶碱治疗后哮喘大鼠血TNF-α及肺病理改变.小儿急救医学，1998，5：157-159.
- 17. Tomita K，Chikuni H，Tokuyasu H，et al.Functional assay of NF-κB translocation into nuclei by laser scanning cytometry：inhibitory effect by dexamethasone or theophylline.Naumyn Schmiedebergs Arch Oharmacol，1999，359：249-255.
