Expression of Fringe in the Asthmatic Mouse Model_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Jie , GUO XuejunCorresponding Author GUO Xuejun

Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University. Shanghai, 200092,China;

Corresponding author：

Keywords：

β1,3-N-acetyl glucosaminyl transfrases; Asthma; Mouse; T cell; Lung

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Objective To investigate the expressions of β1, 3-N-acetyl glucosaminyl transfrases ( Fringe) ( RFNG, LFNG and MFNG) in lung tissues and lung T cells isolated from asthmatic mice, and to explore the role of Fringe in pathogenesis of asthma. Methods Asthmatic BALB/ c mouse model was established by inhalation of ovalbumin after intraperitoneal injection. Meanwhile, the control groups were established by normal saline. Lung tissues were sampled after 24 hours since the last stimulation. T cells were isolated from the lung tissues using percol and NylonFiber. The mRNA expressions of three kinds of Fringe in the lung tissues and lung T cells were examined by reverse transcription-PCR ( RT-PCR) . The protein expressions of Fringe in the lung tissues were detected by Western blot. Results The mRNA expressions of RFNG, LFNG and MFNG were detectable in the lung tissues and lung T cells. The mRNA expressions of RFNG increased in the asthmatic group compared with the control group( lung tissues: 0. 92 ±0. 35 vs 0. 51 ±0. 13, P lt; 0. 01; lung T cells: 0. 33 ±0. 06 vs 0. 18 ±0. 07, P lt; 0. 01) . LFNG mRNA had lower expression level in the asthmatic group( lung tissue: 0. 77 ±0. 32 vs 1. 61 ±0. 31, P lt; 0. 01; lung T cells: 0. 49 ±0. 19 vs 0. 71 ±0. 03, P lt;0. 01) . No difference on the mRNA expression of MFNG was found in the lung tissues( 1. 44 ±0. 29 vs 1. 70 ±0. 44, P gt; 0. 05) . MFNG mRNA expression decreased in the asthmatic group compared with the control group in the T cells( 1. 17 ±0. 04 vs 0. 68 ±0. 07, P lt;0. 05) . The results of western blot were consistent with RT-PCR results of the lung tissues. The expressions of RFNG increased in the asthmatic group( 1. 17 ±0. 04 vs 0. 68 ±0. 07, P lt;0. 05) . The expression of MFNG has no difference between two groups( 8. 10 ±0. 60 vs 9. 12 ±0. 07, P gt;0. 05) . LFNG had a lower expression in the asthmatic group( 4. 11 ±0. 38 vs 6. 41 ±0. 11, P lt; 0. 05) . Conclusion The abnormal expressions of three kinds of Fringe may be involved in the pathogenesis of asthma.

Citation： ZHANG Jie,GUO XuejunCorresponding Author GUO Xuejun,Email guoxjz yahoo. com. cn. Expression of Fringe in the Asthmatic Mouse Model. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(2): 128-132. doi: Copy

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8.	刘春涛,王曾礼,冯玉麟,等.哮喘动物模型气道中白细胞介素5和10的动态变化及其意义.中华结核与呼吸杂志,2000;23:239-242.
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11.	O′Byrne PM.Cytokines or Their Antagonists for the Treatment of Asthma.Chest,2006,130:244-250.
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13.	Kheradmand F,Kiss A,Xu J,et al.A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease1.J Immunol,2002,169:5904-5911.
14.	Georas SN,Guo J,De Fanis U,et al.T-helper cell type-2 regulation in allergic disease.Eur Respir J,2005,26:1119-1137.
15.	Gerard F.Hoyne Notch signaling in the immune system J.Leukoc.Biol.,Dec 2003,74:971.
16.	Sun-Ok Yoon,Xin Zhang,Paul Berner,Bianca Blom,et al.Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J.Immunol.,Jul 2009,183:352 - 358.
17.	Jonathon F.Hutton,Tessa Gargett,Timothy J.Sadlon,et al.Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J.Leukoc.Biol.,Mar 2009,85:445 - 451.
18.	Amsen D,Blander JM,Lee G,et a1.Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells.Cell,2004,ll7:515-526.
19.	Amsen D,Antov A,Jankovic D,et al.Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.Immunity,Jul 2007；27（1）:89-99.
20.	Hozumi K,Abe N,Chiba S,et a1.Active form of notch member can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.J Immunol,2003,170:4973-4979.
21.	Maekawa Y,Tsukumo S,Chiba H,et a1.Delta1-Notch3 Interactions Bias the Functional Differentiation of Activated CD4+ T Cells.Immunity,2003,19:549-559.
22.	Shi S,Stanley P.Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways.PNAS.2003,100:5234-5239.
23.	Okajima T,Irvine KD.Regulation of Notch Signaling by O-Linked Fucose.Cell,2002,111:893-904.
24.	Ge CH,Stanley P.The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.PNAS,2008,105:1539-1544.
25.	Liangtung Y,James TN,Christine Y,et a1.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.

1. Guo XJ,Zhou M,Ren LP,et al.Small interfering RNA mediated knockdown of Notch1 in lung T cells of asthmatic mouse affects T cells differentiation.Chin Med J 2009,122:2647-2651.
2. Gerard FH.Notch signaling in the immune system.J Leukoc Biol,2003,74:971-981.
3. Okajima T,Xu A,Irvine KD.Modulation of Notch-Ligand Binding by Protein O-Fucosyltransferase 1 and Fringe.J Biol Chem,2003;278:42340-42345.
4. Moloney DJ,Shair LH,Lu FM,et al.Mammalian Notch1 Is Modified with Two Unusual Forms of O-Linked Glycosylation Found on Epidermal Growth Factor-like Modules.J Biol Chem,2000,275:9604-9611.
5. Lei L,Xu A,Panin VM,et al.An O-fucose site in the ligand binding domain inhibits Notch activation,2003,130:6411-6421.
6. Xu A,Haines N,Dlugosz M.In Vitro Reconstitution of the Modulation of Drosophila Notch-Ligand Binding by Fringe.J Biol Chem,2007,282:35153-35162.
7. Yang LT,Nichols JT,Yao C,et al.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.
8. 刘春涛,王曾礼,冯玉麟,等.哮喘动物模型气道中白细胞介素5和10的动态变化及其意义.中华结核与呼吸杂志,2000;23:239-242.
9. 周敏,郭雪君,杨敏.支气管哮喘BALB/c小鼠肺组织及肺T细胞中Notch1的表达.上海交通大学学报（医学版）,2007,27:161-164.
10. 杨敏,郭雪君,徐卫国等.Notch配体在哮喘小鼠肺中的表达.中国呼吸与危重监护杂志,2007;6:257-230.
11. O′Byrne PM.Cytokines or Their Antagonists for the Treatment of Asthma.Chest,2006,130:244-250.
12. Pernis AB,Rothman PB.JAK-STAT signaling in asthma.J Clin Invest.2002,109:1279-1283.
13. Kheradmand F,Kiss A,Xu J,et al.A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease1.J Immunol,2002,169:5904-5911.
14. Georas SN,Guo J,De Fanis U,et al.T-helper cell type-2 regulation in allergic disease.Eur Respir J,2005,26:1119-1137.
15. Gerard F.Hoyne Notch signaling in the immune system J.Leukoc.Biol.,Dec 2003,74:971.
16. Sun-Ok Yoon,Xin Zhang,Paul Berner,Bianca Blom,et al.Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J.Immunol.,Jul 2009,183:352 - 358.
17. Jonathon F.Hutton,Tessa Gargett,Timothy J.Sadlon,et al.Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J.Leukoc.Biol.,Mar 2009,85:445 - 451.
18. Amsen D,Blander JM,Lee G,et a1.Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells.Cell,2004,ll7:515-526.
19. Amsen D,Antov A,Jankovic D,et al.Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.Immunity,Jul 2007；27（1）:89-99.
20. Hozumi K,Abe N,Chiba S,et a1.Active form of notch member can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.J Immunol,2003,170:4973-4979.
21. Maekawa Y,Tsukumo S,Chiba H,et a1.Delta1-Notch3 Interactions Bias the Functional Differentiation of Activated CD4+ T Cells.Immunity,2003,19:549-559.
22. Shi S,Stanley P.Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways.PNAS.2003,100:5234-5239.
23. Okajima T,Irvine KD.Regulation of Notch Signaling by O-Linked Fucose.Cell,2002,111:893-904.
24. Ge CH,Stanley P.The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.PNAS,2008,105:1539-1544.
25. Liangtung Y,James TN,Christine Y,et a1.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of Fringe in the Asthmatic Mouse Model

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