THE IMPORTANCE OF TRANSCRIPTION FACTORS STAT6, STAT4, GATA-3 AND T-bet COOPERATION WHEN BRONCHIAL ASTHMA HAS BEEN DIAGNOSED



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Abstract

Lymphocyte signal systems cross-talk interactions present complex net consisting of receptors, enzymes and transcription factors. Using Western blotting for analyzing STAT6, STAT4, GATA-3 and T-bet content in mononuclears, derived from 96 asthma patient and 20 healthy persons, we revealed increase of STAT6 and GATA-3 levels and decrease of STAT4 and T-bet levels in asthma patients, what is obviously may be explained by disturbing of balance in Th1/Th2 regulation interactions. Besides, decrease in STAT4 and T-bet expression in allergic asthma patients was shown, what may indicate malfunction of lL-12-signal-ing pathway in allergic asthma. It may be supposed, that revealed changes in analyzed transcription factors expression levels are connected with clinical and pathogenetic asthma features and probably reflect genetic determination of biology defects.

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About the authors

V I Trophimov

The Saint Petersburg State Medical University named after l. P. Pavlov

Email: trofvi@mail.ru

V N Mineyev

The Saint Petersburg State Medical University named after l. P. Pavlov

L N Sorokina

The Saint Petersburg State Medical University named after l. P. Pavlov

M A Nema

The Saint Petersburg State Medical University named after l. P. Pavlov

V V Lim

The Saint Petersburg State Medical University named after l. P. Pavlov

A V Yeremeyeva

The Saint Petersburg State Medical University named after l. P. Pavlov

References

  1. 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.
  2. Barnes P. J. Role of GATA-3 in allergic diseases // Curr. Mol. Med. — 2008. — Vol. 8, № 5. — P. 330—334.
  3. Pernis A. B., Rothman P. B. JAK-STAT signaling in asthma // J. Clin. Invest. — 2002. — Vol. 109, № 10. — P. 1279—1283.
  4. Shuai K., Liu B. Regulation of JAK-STAT signalling in the immune system // Nature. — 2003. — Vol. 3. — P. 900—911.
  5. Elias J.A., Chun Geun Lee, Tao Zheng et al. New insights into the pathogenesis of asthma // J. Clin. Invest. — 2003. — Vol. 111. — Р. 291—297.
  6. Arakawa S., Hatano Y., Katagiri K. Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis // J. Clin. Exp. Immunol. — 2004. — Vol. 135. — P. 505-510.
  7. Caramori G., Groneberg D., Ito K. et al. New drugs targeting Th2 lymphocytes in asthma // Journal of Occupational Medicine and Toxicology. — 2008. — Vol. 3, Suppl. 1. — P. 1-29.
  8. Barnes P. J. The cytokine network in asthma and chronic obstructive pulmonary disease // J. Clin. Invest. — 2008. — Vol. 118, № 11. — P. 3546-3556.
  9. Szabo S. J., Kim S. T., Costa G. L. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment // Cell. — 2000. — Vol. 100. — P. 655-669.
  10. Минеев В. Н., Сорокина Л. Н., Нема М. А. Влияние IL4 на активность транскрипционного фактора STAT6 в лимфоцитах периферической крови больных бронхиальной астмой // Медицинская иммунология. — 2009. — Т. 11, № 2-3. — С. 177-184.
  11. Минеев В. Н., Сорокина Л. Н., Нема М. А., Трофимов В. И. Экспрессия транскрипционного фактора GATA-3 в лимфоцитах периферической крови больных бронхиальной астмой // Медицинская иммунология. — 2010. — Т. 12, № 1-2. — С. 21-28.
  12. Минеев В. Н., Сорокина Л. Н. Экспрессия транскрипционного фактора T-bet в мононуклеарах периферической крови при бронхиальной астме // Медицинская иммунология. — 2012. — № 1-2. — С. 169-173.
  13. Christodoulopoulos P., Cameron L., Nakamura Y. et al. 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, № 4. — P. 586-591.
  14. Cornejo-Garcia J. A., Fernandez T. D., Torres M. J. et al. Differential cytokine and transcription factor expression in patients with allergic reactions to drugs // Allergy. — 2007. — Vol. 62, № 12. — P. 1429-1438.
  15. Mantel P.-Y., Kuipers H., Boyman O. et al. GATA3-Driven Th2 Responses Inhibit TGF-b1-Induced FOXP3 Expression and the Formation of Regulatory T Cells // J. PLoS. Biology. — 2007. — Vol. 5, Issue 12. — P. 2847-2861.
  16. Taha R., Hamid Q., Cameron L., Olivenstein R. T-helper type-2 cytokine receptors and associated transcription factors GATA-3, c-MAF, and signal transducer and activator of transcription factor-6 in induced sputum of atopic asthmatic patients. // Chest. — 2003. — Vol. 123. — P. 2074-2082.
  17. Wurster A. L., Tanaka T., Grusby M. J. The biology of Stat4 and STAT6 // Oncogene. — 2000. — Vol. 19. — P. 2577-2584.
  18. Ko F. W. S., Lun S. W. M., Wong C. K. et al. Decreased T-bet expression and changes in chemokine levels in adults with asthma // J. Clin. Exp. Immunol. — 2007. — Vol. 147. — P. 526-532.

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Copyright (c) 2013 Trophimov V.I., Mineyev V.N., Sorokina L.N., Nema M.A., Lim V.V., Yeremeyeva A.V.

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