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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.1 P.22-28

http://doi.org/10.1631/jzus.B0820226


RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model


Author(s):  Shao-xing CHEN, Feng-ying HUANG, Guang-hong TAN, Cai-chun WANG, Yong-hao HUANG, Hua WANG, Song-lin ZHOU, Fan CHEN, Ying-ying LIN, Jun-bao LIU

Affiliation(s):  Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571101, China; more

Corresponding email(s):   scihai@126.com

Key Words:  Interleukin-5 (IL-5), Small interfering RNA (siRNA), Airway hyperresponsiveness (AHR), Allergy, Lentivirus


Shao-xing CHEN, Feng-ying HUANG, Guang-hong TAN, Cai-chun WANG, Yong-hao HUANG, Hua WANG, Song-lin ZHOU, Fan CHEN, Ying-ying LIN, Jun-bao LIU. RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model[J]. Journal of Zhejiang University Science B, 2009, 10(1): 22-28.

@article{title="RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model",
author="Shao-xing CHEN, Feng-ying HUANG, Guang-hong TAN, Cai-chun WANG, Yong-hao HUANG, Hua WANG, Song-lin ZHOU, Fan CHEN, Ying-ying LIN, Jun-bao LIU",
journal="Journal of Zhejiang University Science B",
volume="10",
number="1",
pages="22-28",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820226"
}

%0 Journal Article
%T RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model
%A Shao-xing CHEN
%A Feng-ying HUANG
%A Guang-hong TAN
%A Cai-chun WANG
%A Yong-hao HUANG
%A Hua WANG
%A Song-lin ZHOU
%A Fan CHEN
%A Ying-ying LIN
%A Jun-bao LIU
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 1
%P 22-28
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820226

TY - JOUR
T1 - RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model
A1 - Shao-xing CHEN
A1 - Feng-ying HUANG
A1 - Guang-hong TAN
A1 - Cai-chun WANG
A1 - Yong-hao HUANG
A1 - Hua WANG
A1 - Song-lin ZHOU
A1 - Fan CHEN
A1 - Ying-ying LIN
A1 - Jun-bao LIU
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 1
SP - 22
EP - 28
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820226


Abstract: 
interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5×106 IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Barthel, S.R., Johansson, M.W., McNamee, D.M., Deane, F., Mosher, D.F., 2008. Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma. J. Leukoc. Biol., 83(1):1-12.

[2] Bentley, A.M., Menz, G., Storz, C., Robinson, D.S., Bradley, B., Jeffery, P.K., Durham, S.R., Kay, A.B., 1992. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am. Rev. Respir. Dis., 146(2):500-506.

[3] Blyth, D.I., Wharton, T.F., Pedrick, M.S., Tony, J., Savage, T.J., Sanjar, S., 2000. Airway subepithelial fibrosis in a murine model of atopic asthma. Suppression by dexamethasone or anti-interleukin-5 antibody. Am. J. Respir. Cell Mol. Biol., 23(2):241-246.

[4] Busse, W.W., Lemanske, R.F., 2001. Asthma. N. Engl. J. Med., 344(5):350-362.

[5] Cho, J.Y., Miller, M., Baek, K.J., Han, J.W., Nayar, J., Lee, S.Y., McElwain, K., McElwain, S., Friedman, S., Broide, D.H., 2004. Inhibition of airway remodeling in IL-5-deficient mice. J. Clin. Invest., 113(4):551-560.

[6] Clutterbuck, E.J., Hirst, E.M., Sanderson, C.J., 1989. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood, 73(6):1504-1512.

[7] Durham, S.R., Loegering, D.A., Dunnette, S., Gleich, G.J., Kay, A.B., 1989. Blood eosinophils and eosinophil-derived proteins in allergic asthma. J. Allergy Clin. Immunol., 84(6):931-936.

[8] Fixman, E.D., Stewart, A., Martin, J.G., 2007. Basic mechanisms of development of airway structural changes in asthma. Eur. Respir. J., 29(2):379-389.

[9] Garlisi, C.G., Kung, T.T., Wang, P., Minnicozzi, M., Umland, S.P., Chapman, R.W., Stelts, D., Crawley, Y., Falcone, A., Myers, J.G., et al., 1999. Effects of chronic anti-interleukin-5 monoclonal antibody treatment in a murine model of pulmonary inflammation. Am. J. Respir. Cell Mol. Biol., 20(2):248-255.

[10] Gleich, G.J., 1990. The eosinophil and bronchial asthma: current understanding. J. Allergy Clin. Immunol., 85(2): 422-436.

[11] Hakonarson, H., Maskeri, N., Carter, C., Chuang, S., Grunstein, M.M., 1999a. Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J. Clin. Invest., 104(5):657-667.

[12] Hakonarson, H., Maskeri, N., Carter, C., Grunstein, M.M., 1999b. Regulation of Th1- and Th2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. J. Clin. Invest., 103(7):1077-1087.

[13] Hamelmann, E., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G.L., Irvin, C.G., Gelfand, E.W., 1997. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am. J. Respir. Crit. Care Med., 156(3):766-775.

[14] Hertz, M., Mahalingam, S., Dalum, I., Klysner, S., Mattes, J., Neisig, A., Mouritsen, S., Foster, P.S., Gautam, A., 2001. Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma. J. Immunol., 167(7):3792-3799.

[15] Humbert, M., 1996. Pro-eosinophilic cytokines in asthma. Clin. Exp. Allergy, 26(2):123-127.

[16] Humbles, A.A., Lloyd, C.M., McMillan, S.J., Friend, D.S., Xanthou, G., McKenna, E.E., Ghiran S., Gerard, N.P., Yu, C., Stuart, H., et al., 2004. A critical role for eosinophils in allergic airways remodeling. Science, 305(5691): 1776-1779.

[17] Jiang, Y.F., Zhao, F.D., Li, X.B., Ning, Y.X., Zhi, X.L., Qian, R.Z., Yin, L.H., 2008. Effects of RNA interference-induced tryptase down-regulation in P815 cells on IL-6 and TNF-α release of endothelial cells. J. Zhejiang Univ. Sci. B, 9(8):656-661.

[18] Karras, J.G., McGraw, K., McKay, R.A., Cooper, S.R., Lerner, D., Lu, T., Walker, C., Dean, N.M., Monia, B.P., 2000. Inhibition of antigen-induced eosinophilia and late phase airway hyperresponsiveness by an IL-5 antisense oligonucleotide in mouse models of asthma. J. Immunol., 164(10):5409-5415.

[19] Kroegel, C., Virchow, J.C., Luttmann, W., Walker, C., Warner, J.A., 1994. Pulmonary immune cells in health and disease: the eosinophil leucocyte. Part I. Eur. Respir. J., 7(3): 519-543.

[20] Leckie, M.J., Brinke, A., Khan, J., Diamant, Z., O′Connor, B.J., Walls, C.M., Mathur, A.K., Cowley, H.C., Chung, K.F., Djukanovic, R., et al., 2000. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet, 356(9248):2144-2148.

[21] Mattes, J., Foster, P.S., 2003. Regulation of eosinophil migration and Th2 cell function by IL-5 and eotaxin. Curr. Drug Targets Inflamm. Allergy, 2(2):169-174.

[22] Menzies-Gow, A., Flood-Page, P., Sehmi, R., Burman, J., Hamid, Q., Robinson, D.S., Kay, A.B., Denburg, J., 2003. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J. Allergy Clin. Immunol., 111(4):714-719.

[23] Popescu, F.D., 2005. Antisense- and RNA interference-based therapeutic strategies in allergy. J. Cell. Mol. Med., 9(4):840-853.

[24] Robinson, D., Hamid, Q., Ying, S., Tsicopoulos, A., Barkans, J., Bentley, A.M., Corrigan, C., Durham, S.R., Kay, A.B., 1992. Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl. J. Med., 326(5):298-304.

[25] Robinson, D., Hamid, Q., Bentley, A., Ying, S., Kay, A.B., 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(2):313-324.

[26] Sanderson, C.J., 1992. Interleukin-5, eosinophils, and disease. Blood, 79(12):3101-3109.

[27] Shen, H.H., Ochkur, S.I., McGarry, M.P., Crosby, J.R., Hines, E.M., Borchers, M.T., Wang, H., Biechelle, T.L., O′Neill, K.R., Ansay, T.L., et al., 2003. A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse. J. Immunol., 170(6):3296-3305.

[28] Simon, D., Braathen, L.R., Simon, H.U., 2005. Anti-interleukin-5 antibody therapy in eosinophilic diseases. Pathobiology, 72(6):287-292.

[29] Sugita, M., Kuribayashi, K., Nakagomi, T., Miyata, S., Matsuyama, T., Kitada, O., 2003. Allergic bronchial asthma: airway inflammation and hyperresponsiveness. Intern. Med., 42(8):636-643.

[30] Sutton, S.A., Assa'ad, A.H., Rothenberg, M.E., 2005. Anti-IL-5 and hypereosinophilic syndromes. Clin. Immunol., 115(1):51-60.

[31] Tan, G.H., Su, J.M., Wang, C.C., Huang, F.Y., Wang, H., Huang, Y.H., Lin, Y.Y., 2008. A recombinant DNA plasmid encoding the human interleukin-5 breaks immunological tolerance and inhibits airway inflammation in a murine model of asthma. Int. Arch. Allergy Immunol., 145(4):313-323.

[32] Tournoy, K.G., Kips, J.C., Pauwels, R.A., 2001. The allergen-induced airway hyperresponsiveness in a human-mouse chimera model of asthma is T cell and IL-4 and IL-5 dependent. J. Immunol., 166(11):6982-6991.

[33] Walter, M.J., Holtzman, M.J., 2005. A centennial history of research on asthma pathogenesis. Am. J. Respir. Cell Mol. Biol., 32(6):483-489.

[34] Woodruff, P.G., Khashayar, R., Lazarus, S.C., Janson, S., Avila, P., Boushey, H.A., Segal, M., Fahy, J.V., 2001. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J. Allergy Clin. Immunol., 108(5):753-758.

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