EFFECTS OF IL-4 UPON THE ACTIVITY OF STAT6 TRANSCRIPTION FACTOR IN PERIPHERAL BLOOD LYMPHOCYTES IN BRONCHIAL ASTHMA
https://doi.org/10.15789/1563-0625-2009-2-3-177-184
Abstract
Abstract. The aim of the study is to specify the levels of STAT6, and phospho-STAT6 under the influence of IL-4 in patients with bronchial asthma (BA). The samples from ten healthy controls and thirty-three BA patients with allergic and non-allergic clinical forms of different severity were under investigation. Peripheral blood lymphocytes were treated with 10 ng/ml of IL-4 (Sigma Aldrich, USA) for 1 h. Then the proteins (STAT6 and phospho-STAT6) expressed in peripheral lymphocytes were analyzed by Western blot of cell lysates. Preparation of the cell lysates and Western blotting were carried out using standard procedures. Antibodies against phospho-STAT6 and STAT6 (10 ng/ml) were used (Cell Signaling, USA). Levels of thespecific proteins were standardized according to β-actin (Cell Signaling, USA). Treatment with IL-4 caused an increase of phospho-STAT6 levels in lymphocytes of all BA patients, as compared with control group. In allergic BA, the phospho-STAT6 levels were significantly higher than in non-allergic clinical forms. Expression of STAT6 in lymphocytes of patients with severe BA was significantly higher, as compared to BA of moderate severity. An IL-4-induced activation of the STAT6 transcription factor was revealed in an in vitro system, being mostly expressed in allergic BA. The level of STAT6 may serve as a BA severity index. This study was supported by a «Scholarship of the Year» grant from the St. Petersburg State Medical I. Pavlov University (2007).
About the Authors
V. N. Mineev
Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
Russian Federation
Russian Federation
L. N. Sorokina
Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
Russian Federation
Russian Federation
M. A. Nyoma
Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
Russian Federation
Russian Federation
References
1. Лимфоциты: методы: Пер. с англ. / Под ред. Дж. Клауса. – М.: Мир, 1990. – 395 с.
2. Минеев В.Н., Нестерович И.И., Лалаева Т.М., Иванова В.В., Яблонская В.Н., Булатова Н.Ю., Лукашевская Н.Н., Сорокина Л.Н., Рабик Ю.Д., Супранович И.Ю., Волченкова О.С., Болотина Н.В. Сигнальные системы при бронхиальной астме // Ученые записки СПбГМУ им. акад. И.П. Павлова. – 2001. – Т. 8, № 1. – С. 17-21.
3. Минеев В.Н., Сорокина Л.Н. Современные представления о JAK-STAT системе как новой сигнальной системе и ее нарушениях при иммунной патологии (Часть I) // Аллергология. – 2005. – № 4. – С. 38-44.
4. Минеев В.Н., Сорокина Л.Н. Современные представления о JAK-STAT системе как новой сигнальной системе и ее нарушениях при иммунной патологии: механизмы негативной регуляции (Часть II) // Аллергология. – 2006. – № 1. – С. 49-55.
5. Минеев В.Н., Сорокина Л.Н. Экспрессия STAT6 в лимфоцитах периферической крови больных аллергической бронхиальной астмой // Медицинская иммунология. – 2007. – Т. 9, № 4-5. – С. 405-410.
6. Фрейдлин И.С., Тотолян А.А. Иммунологические механизмы аллергических реакций. // Общая аллергология. – Т. 1. – СПб., 2001. – С. 169-381.
7. Biola A., Andreau K., David M., Sturm M., Haake M., Bertoglio J., Pallardy M. The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes // FEBS Letters – 2000. – Vol. 487. – P. 229-233.
8. Caramori G., Lim S., Ito K., Tomita K., Oates T., Jazrawi E., Chung K.F., Barnes P.J., Adcock I.M. Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies // Eur. Respir. J. – 2001. – Vol. 18. – P. 466-473.
9. Christodoulopoulos P., Cameron L., Nakamura Y., Lemi re C., Muro S., Dugas M., Boulet L-P., Laviolette M., Olivenstein R., Hamid Q. Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression // J. Allergy Clin. Immunol. – 2001. – Vol. 107, N 4. – P. 586–591.
10. Chung K. F., Barnes P. J. Cytokines in asthma // Thorax. – 1999. – Vol. 54. – P. 825-857.
11. Darnell J.E., Kerr I.M., Stark G.R. Jak –STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins // Science. – 1994. – Vol. 64. – Р. 1415-1421.
12. Diel F., Borck H., Horr B. Distinct responses to histamine of STAT1 and STAT6 phosphoregulation in human T helper lymphocytes // Inflamm. Res. – 2004. – Vol. 53., N 1. – P. 19-20.
13. Herrick Ch.A., Bottomly K. To respond or not to respond: T cells in allergic asthma // Nature Reviews / Immunology. – 2003. – Vol. 3. – P. 1-8.
14. Kaplan M.H., Schindler U., Smiley S.T., Grusby M.J. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells // Immunity. – 1996. – Vol. 4. – P. 313-319.
15. Kharmate G., Liu Z., Patterson E., Khan M.M. Histamine affects STAT6 phosphorylation via its effects on IL-4 secretion: role of H1 receptors in the regulation of IL-4 production // Int. Immunophrmacol. – 2007. – Vol.7, N 3. – P. 277–286.
16. Kuperman D., Schofield B., Wills-Karp M., Grusby M.J. Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production // J. Exp. Med. – 1998. – Vol.187. – P. 939-948.
17. Leonard C., Tormey V., Burke C., Poulter L.W. Allergen-induced cytokine production in atopic disease and its relationship to disease severity // Am. J. Respir. Cell Mol. Biol. – 1997. – Vol. 17. – P. 368 - 375.
18. Mullings, R.E., Wilson S.J., Puddicombe S.M., Lordan J.L., Bucchieri F., Djukanović R., Howarth P.H., Harper S., Holgate S.T., Davies D.E. Signal transducer and activator of transcription 6 (STAT - 6) expression and function in asthmatic bronchial epithelium // J. Allergy Clin. Immunol. – 2001. – Vol. 108, N 5. – P. 832-838.
19. Murray P.J. The JAK-STAT signaling pathway: input and output integration // J. Immunol. – 2007. – Vol. 178. – P. 2623-2629.
20. Nelson G., Wilde G.J.C., Spiller D.G., Kennedy S.M., Ray D.W., Sullivan E., Unitt J.F., White R.H. NF-kB signalling is inhibited by glucocorticoid receptor and STAT6 via distinct mechanisms // Journal of Cell Science – 2003. – Vol.116. – P. 2495 - 2503.
21. O’Shea J. J., Park H., Pesu M., Borie D., Changelian P. New strategies for immunosuppression: interfering with cytokines by targeting the Jak –Stat pathway // Curr. Opin. Rheumatol. – 2005. – Vol. 17, N 3. – P. 305-311.
22. Pernis A.B., Rothman P.B. JAK-STAT signaling in asthma // J. Clin. Invest. – 2002. – Vol. 109, N 10. – P. 1279-1283.
23. Rawlings J.S., Rosler K.M., Harrison D.A. The JAK-STAT signaling pathway // J. Cell Science. – 2004. – Vol. 117. – P. 1281-1283.
24. Shi H.Z., Deng J.M., Xu H., Nong Z.X., Xiao C.Q., Liu Z.M., Qin S.M., Jiang H.X., Liu G.N., Chen Y.Q. Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics // Am. J. Respir. Crit. Care Med. – 1998. – Vol. 157. – P. 1818-1821.
25. Shuai K., Liu B. Regulation of JAK-STAT signalling in the immune system // Nature. – 2003. – Vol. 3. – P. 900-911.
26. Steinke J.W., Borish L. Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. // J. Respir. Res. – 2001. – Vol. 2. – P. 66-70.
27. Walker C., Bauer W., Braun R.K., Menz G., Braun P., Schwarz F., Hansel T.T., Villiger B. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with Eosinophilia // Am. J. Respir. Crit. Care Med. – 1994. – Vol. 150. – P. 1038-1048.
Review
For citations:
Mineev V.N., Sorokina L.N., Nyoma M.A. EFFECTS OF IL-4 UPON THE ACTIVITY OF STAT6 TRANSCRIPTION FACTOR IN PERIPHERAL BLOOD LYMPHOCYTES IN BRONCHIAL ASTHMA. Medical Immunology (Russia). 2009;11(2-3):177-184. (In Russ.) https://doi.org/10.15789/1563-0625-2009-2-3-177-184
Views:
923
Email this article 