한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)

  • 제38권1호
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  • Pages.93-104
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  • 2010
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  • 1598-642X(pISSN)
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  • 2234-7305(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지

프랑킨센스 에센셜 오일 흡입이 OVA로 유도된 알러지성 천식 모델 생쥐에 미치는 영향

The Effect of Nebulized Frankincense Essential Oil in an OVA-Induced Allergic Asthma Mouse Model

  • 이혜연 (건국대학교 대학원 생물공학과) ;
  • 김금란 (건국대학교 대학원 생물공학과) ;
  • 강상모 (건국대학교 미생물공학과)
  • Lee, Hye-Youn (Department of Bioengineering Graduate School at Konkuk University) ;
  • Kim, Kum-Ran (Department of Bioengineering Graduate School at Konkuk University) ;
  • Kang, Sang-Mo (Department of Microbial Engineering, Konkuk University)
  • 투고 : 2010.01.15
  • 심사 : 2010.03.03
  • 발행 : 2010.03.28
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초록

프랑킨센스 에센셜 오일(BSEO)이 알러지성 천식 생쥐 모델의 폐, BALF 및 PBMC 내 면역세포 변화에 미치는 영향을 조사하였다. 본 연구는 Balb/c 생쥐를 이용하여 실험 1일에 $100\;{\mu}g$ ovalbumin (OVA)을 복강 내 투여하고, 실험 14일에 $50\;{\mu}g$ OVA를 기도 내 투여하여 감작시킨 후 OVA를 반복 흡입시켜 천식을 유발하였다. 천식 유발 생쥐군에 0.3% BSEO를 8주간, 1주에 3회, 1회에 30분간 nebulizer로 흡입시켰고, 실험일로부터 총 12주 후에 살처분시켜 폐, 기관지 폐포 세척액 (bronchoalveolar lavage fluid; BALF), 말초혈액단핵세포 (peripheral blood mononuc1ear cell; PBMC)를 분리하여 조직 내의 면역세포 변화를 관찰하였다. 본 연구 결과 알러지성 천식 유발 생쥐에서 기관지 수축제에 대한 기도 과민성반응이 천연 아로마 에센셜 오일군인 Bergamot군, Eucalyptus군, Chamomile군, Marjoram군, 및 Frankincense군 중 Frankincense군에서 효과적으로 억제됨을 확인하였다. 또한 알러지성 천식유발로 증가한 폐무게, 총폐포수, BALF수, MNL, DLN수가 억제됨을 확인하였다. BSEO는 알러지성 천적 모델 생쥐의 폐 조직 내의 $CD3e^+/CD19^-$, $B220^+/CD23^+$, $CD11b^+/Gr-1^+$ 세포 비율을 억제하였으며 BALF 내의 $CD4^+/CD8^-$, $B220^+/CD23^+$, $CD3e^+/CCR3^+$ 세포비율을 억제하였다. 또한 PBMC내 $CD3e^+/CD19^-$, $CD3^+/CD69^+$, $B220^+/CD23^+$ 세포비율을 억제하였다. 이러한 결과는 BSEO가 각 조직내의 면역세포의 활성 억제를 통한 면역조절작용으로 알러지성 천식의 치료에 효과적일 것으로 사료되었다.

In this study, we investigated the effects of frankincense essential oil (BSEO) on the immune cell change in the lung, BALF and PBMC using a mouse model of asthma. BALB/c mice after intraperitoneal OVA sensitization (day 1) were challenged intratracheally with OVA on day 14. Then, the asthma was induced by repeated OVA inhalation challenged. The asthma induced mice group inhaled 0.3% BSEO for 30 minutes per trial, three times a week, for 8 weeks using the nebulizer. After 12 weeks from the experiment, the mice was killed and the lung, bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) were obtained. Next, the change of immune cells inside the separated tissues was observed to identity the effects of BSEO on the allergic asthma mice. In conclusion, the hypersensitive reaction of airway to the bronchoconstrictor in the allergic asthma induced mice was effectively suppressed in Frankincense group, in Bermagot, Eucalyptus, Chamomile, Marjoram and Frankincense groups, the natural aromatic essential oil groups. Furthermore, it was also confirmed that the weight of lung, total number of alveolus cells and the number of BALF, MNL and DLN increased after inducing allergic asthma were reduced. BSEO suppressed the percentage of $CD3e^+/CD19^-$, $B220^+/CD23^+$ and $CD11b^+/Gr-1^+$ cells in the lung tissue of allergic asthma mice. Moreover, BSEO also reduced the percentage of $CD4^+/CD8^-$, $B220^+/CD23^+$ and $CD3^+/CCR3^+$ cells in BALF. In addition, the percentage of $CD3e^+/CD19^-$, $CD3^+/CD69^+$ and $B220^+/CD23^+$ cells in PBMC was reduced. The results of this study indicate that BSEO would be effective to treat allergic asthma by the immune control suppressing the activity of immune cells in each tissue.

키워드

참고문헌

  1. Ammon, H. P. 2006. Boswellic acids in chronic inflammatory diseases. Planta. Med. 72: 1100-1116. https://doi.org/10.1055/s-2006-947227
  2. Arnold, V., Balkow, S., Staats, R., Matthys, H., Luttmann, W., and Virchow, J. C., Jr. 2000. Increase in perforin-positive peripheral blood lymphocytes in extrinsic and intrinsic asthma. Pneumologie. 54: 468-473. https://doi.org/10.1055/s-2000-7690
  3. Baraldo, S., Lokar Oliani, K., Turato, G., Zuin, R., and Saetta, M. 2007. The Role of Lymphocytes in the Pathogenesis of Asthma and COPD. Curr. Med. Chem. 14: 2250-2256. https://doi.org/10.2174/092986707781696573
  4. Barnes, P. J., Jonsson, B., and Klim, J. B. 1996. The costs of asthma. Eur. Respir. J. 9: 636-642. https://doi.org/10.1183/09031936.96.09040636
  5. Basyigit, I., Yildiz, F., Ozkara, S. K., Boyaci, H., and Ilgazli, A. 2004. Inhaled corticosteroid effects both eosinophilic and non-eosinophilic inflammation in asthmatic patients. Mediators Inflamm. 13: 285-291. https://doi.org/10.1080/09629350400003118
  6. Beasley, R., Roche, W. R., Roberts, J. A., and Holgate, S. T. 1989. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am. Rev. Respir. Dis. 139: 806-817. https://doi.org/10.1164/ajrccm/139.3.806
  7. Borgonovo, B., Casorati, G., Frittoli, E., Gaffi, D., Crimi, E., and Burastero, S. E. 1997. Recruitment of circulating allergen-specific T lymphocytes to the lung on allergen challenge in asthma. J. Allergy Clin. Immunol. 100: 669-678. https://doi.org/10.1016/S0091-6749(97)70172-6
  8. Bousquet, J., Chanez, P., Lacoste, J. Y., Barneon, G., Ghavanian, N., Enander, I., Venge, P., Ahlstedt, S., Simony-Lafontaine, J., Godard, P., and et al. 1990. Eosinophilic inflammation in asthma. N. Engl. J. Med. 323: 1033-1039. https://doi.org/10.1056/NEJM199010113231505
  9. Bratke, K., Bottcher, B., Leeder, K., Schmidt, S., Kupper, M., Virchow, J. C., Jr., and Luttmann, W. 2004. Increase in granzyme $B^+$ lymphocytes and soluble granzyme B in bronchoalveolar lavage of allergen challenged patients with atopic asthma. Clin. Exp. Immunol. 136: 542-548. https://doi.org/10.1111/j.1365-2249.2004.02468.x
  10. Busse, W. W., and Lemanske, R. F., Jr. 2001. Asthma. N. Engl. J. Med. 344: 350-362. https://doi.org/10.1056/NEJM200102013440507
  11. D'Amato, G., Bucchioni, E., Oldani, V., and Canonica, W. 2006. Treating Moderate-to-Severe Allergic Asthma with a Recombinant Humanized Anti-IgE Monoclonal Antibody (Omalizumab). Treat. Respir. Med. 5: 393-398. https://doi.org/10.2165/00151829-200605060-00004
  12. de Heer, H. J., Hammad, H., Soullie, T., Hijdra, D., Vos, N., Willart, M. A., Hoogsteden, H. C., and Lambrecht, B. N. 2004. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 200: 89-98. https://doi.org/10.1084/jem.20040035
  13. Devos, S., Cormont, F., Vrtala, S., Hooghe-Peters, E., Pirson, F., and Snick, J. 2006. Allergen-induced interleukin-9 production in vitro: correlation with atopy in human adults and comparison with interleukin-5 and interleukin-13. Clin. Exp. Allergy. 36: 174-182. https://doi.org/10.1111/j.1365-2222.2006.02422.x
  14. Dolecek, C., Steinberger, P., Susani, M., Kraft, D., Valenta, R., and Boltz-Nitulescu, G. 1995. Effects of IL-4 and IL-13 on total and allergen specific IgE production by cultured PBMC from allergic patients determined with recombinant pollen allergens. Clin. Exp. Allergy. 25: 879-889. https://doi.org/10.1111/j.1365-2222.1995.tb00031.x
  15. Dorshkind, K., Narayanan, R., and Landreth, K. S. 1992. Regulatory cells and cytokines involved in primary B lymphocyte production. Adv. Exp. Med. Biol. 323: 119-123. https://doi.org/10.1007/978-1-4615-3396-2_15
  16. Duan, W., Chan, J. H., Wong, C. H., Leung, B. P., and Wong, W. S. 2004. Anti-inflammatory effects of mitogenactivated protein kinase kinase inhibitor U0126 in an asthma mouse model. J. Immunol. 172: 7053-7059.
  17. Erin, E. M., Williams, T. J., Barnes, P. J., and Hansel, T. T. 2002. Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Curr. Drug Targets Inflamm. Allergy. 1: 201-214.
  18. Furusho, S., Myou, S., Fujimura, M., Kita, T., Yasui, M., Kasahara, K., Nakao, S., Takehara, K., and Sato, S. 2006. Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma. Clin. Exp. Allergy. 36: 1294-1302. https://doi.org/10.1111/j.1365-2222.2006.02568.x
  19. Gaga, M., Zervas, E., Grivas, S., Castro, M., and Chanez, P. 2007. Evaluation and management of severe asthma. Curr. Med. Chem. 14: 1049-1059. https://doi.org/10.2174/092986707780362961
  20. Gilroy, D. W., Lawrence, T., Perretti, M., and Rossi, A. G. 2004. Inflammatory resolution: new opportunities for drug discovery. Nat. Rev. Drug Discov. 3: 401-416. https://doi.org/10.1038/nrd1383
  21. Hamelmann, E., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G. L., Irvin, C. G., and Gelfand, E. W. 1997. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am. J. Respir. Crit. Care Med. 156: 766-775. https://doi.org/10.1164/ajrccm.156.3.9606031
  22. Hammad, H., Kool, M., Soullie, T., Narumiya, S., Trottein, F., Hoogsteden, H. C., and Lambrecht, B. N. 2007. Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells. J. Exp. Med. 204: 357-367. https://doi.org/10.1084/jem.20061196
  23. Herrick, C. A., and Bottomly, K. 2003. To respond or not to respond: T cells in allergic asthma. Nat. Rev. Immunol. 3: 405-412. https://doi.org/10.1038/nri1084
  24. Idzko, M., Hammad, H., van Nimwegen, M., Kool, M., Muller, T., Soullie, T., Willart, M. A., Hijdra, D., Hoogsteden, H. C., and Lambrecht, B. N. 2006. Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. J. Clin. Invest. 116: 2935-2944. https://doi.org/10.1172/JCI28295
  25. Keramidaris, E., Merson, T. D., Steeber, D. A., Tedder, T. F., and Tang, M. L. 2001. L-selectin and intercellular adhesion molecule 1 mediate lymphocyte migration to the inflamed airway/lung during an allergic inflammatory response in an animal model of asthma. J. Allergy Clin. Immunol. 107: 734-738. https://doi.org/10.1067/mai.2001.114050
  26. Kibe, A., Inoue, H., Fukuyama, S., Machida, K., Matsumoto, K., Koto, H., Ikegami, T., Aizawa, H., and Hara, N. 2003. Differential regulation by glucocorticoid of interleukin-13-induced eosinophilia, hyperresponsiveness, and goblet cell hyperplasia in mouse airways. Am. J. Respir. Crit. Care Med. 167: 50-56. https://doi.org/10.1164/rccm.2110084
  27. Kung, T. T., Stelts, D., Zurcher, J. A., Watnick, A. S., Jones, H., Mauser, P. J., Fernandez, X., Umland, S., Kreutner, W., Chapman, R. W., and et al. 1994. Mechanisms of allergic pulmonary eosinophilia in the mouse. J. Allergy Clin. Immunol. 94: 1217-1224. https://doi.org/10.1016/0091-6749(94)90335-2
  28. Lagging, E., van Hage-Hamsten, M., Gronneberg, R., Elfman, L., and Harfast, B. 1998. Cytokine production in PBMC from allergics and non-allergics following in vitro allergen stimulation. Immunol. Lett. 60: 45-49. https://doi.org/10.1016/S0165-2478(97)00130-2
  29. Laky, K., Fleischacker, C., and Fowlkes, B. J. 2006. TCR and Notch signaling in CD4 and CD8 T-cell development. Immunol. Rev. 209: 274-283. https://doi.org/10.1111/j.0105-2896.2006.00358.x
  30. Lee, H.-Y., Yun, M.-Y., and Kang, S.-M. 2008. Antiinflammatory effect of Boswellia sacra (Frankincense) essential oil in a mouse model of allergic asthma. Kor. J. Microbiol. Biotechnol. 36: 343-352.
  31. Li, Y. F., Tsao, Y. H., Gauderman, W. J., Conti, D. V., Avol, E., Dubeau, L., and Gilliland, F. D. 2005. Intercellular adhesion molecule-1 and childhood asthma. Hum. Genet. 117: 476-484.
  32. Mitzner, W., and Tankersley, C. 1998. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am. J. Respir. Crit. Care Med. 158: 340-341. https://doi.org/10.1164/ajrccm.158.1.let1
  33. Moverare, R., Rak, S., and Elfman, L. 1998. Allergenspecific increase in interleukin (IL)-4 and IL-5 secretion from peripheral blood mononuclear cells during birch-pollen immunotherapy. Allergy. 53: 275-281. https://doi.org/10.1111/j.1398-9995.1998.tb03887.x
  34. Nomura, A., Uchida, Y., Sakamoto, T., Ishii, Y., Masuyama, K., Morishima, Y., Hirano, K., and Sekizawa, K. 2002. Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-beta. Clin. Exp. Allergy. 32: 860-865. https://doi.org/10.1046/j.1365-2745.2002.01404.x
  35. O'Garra, A., and Murphy, K. 1994. Role of cytokines in determining T-lymphocyte function. Curr. Opin. Immunol. 6: 458-466. https://doi.org/10.1016/0952-7915(94)90128-7
  36. Ram, A., Das, M., Gangal, S. V., and Ghosh, B. 2004. Para- Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice. Int. Immunopharmacol. 4: 1697-1707. https://doi.org/10.1016/j.intimp.2004.08.001
  37. Renauld, J. C. 2001. New insights into the role of cytokines in asthma. J. Clin. Pathol. 54: 577-589. https://doi.org/10.1136/jcp.54.8.577
  38. Robinson, D., Hamid, Q., Bentley, A., Ying, S., Kay, A. B., and Durham, S. R. 1993. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J. Allergy Clin. Immunol. 92: 313-324. https://doi.org/10.1016/0091-6749(93)90175-F
  39. Roh, G. S., Seo, S. W., Yeo, S., Lee, J. M., Choi, J. W., Kim, E., Shin, Y., Cho, C., Bae, H., Jung, S. K., and Kwack, K. 2005. Efficacy of a traditional Korean medicine, Chung- Sang-Bo-Ha-Tang, in a murine model of chronic asthma. Int. Immunopharmacol. 5: 427-436. https://doi.org/10.1016/j.intimp.2004.09.036
  40. Roh, S. S., Kim, S. H., Lee, Y. C., and Seo, Y. B. 2008. Effects of radix adenophorae and cyclosporine A on an OVA-induced murine model of asthma by suppressing to T cells activity, eosinophilia, and bronchial hyperresponsiveness. Mediators Inflamm. 2008: 781425.
  41. Samson, K. T., Minoguchi, K., Tanaka, A., Oda, N., Yokoe, T., Yamamoto, Y., Yamamoto, M., Ohta, S., and Adachi, M. 2006. Inhibitory effects of fluvastatin on cytokine and chemokine production by peripheral blood mononuclear cells in patients with allergic asthma. Clin. Exp. Allergy. 36: 475-482. https://doi.org/10.1111/j.1365-2222.2006.02470.x
  42. Sancho, D., Gomez, M., and Sanchez-Madrid, F. 2005. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol. 26: 136-140. https://doi.org/10.1016/j.it.2004.12.006
  43. Zhou, M., Dong, M., Wu, Y., Wang, L., and Yue, B. 2006. The expression and significance of eotaxin gene in nasal mucosa and CCR3 in bone marrow in model of allergic rhinitis. Lin. Chuang. Er. Bi. Yan. Hou. Ke. Za. Zhi. 20: 227-230.