Cooperative interactions of Fохр3, с-Maf, GATA3 and T-bet transcription factors in bronchial asthma

This study was aimed at evaluation of pathogenic role of Fохр3, GATA-3, c-Maf, and T-bet transcription factors in asthma.

Methods. 47 healthy individuals and 82 patients with bronchial asthma including 42 patients with allergic asthma (ABA) and 40 patients with non-allergic asthma (NABA) participated in the study. An expression of mRNA of Fохр3 (forkhead box P3), с-Maf (transcription factor Maf), GATA3 (GATA-binding protein 3), and T-bet (T-box protein, TBX21) transcription factors was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Serum concentrations of IgE and cytokines (IL-4, IL-13, IL-17, IL-6, IFN-γ) were measured using ELISA method.

Results. An imbalance in Th1/Th2/Foxp3+Treg and Th17/Foxp3+Treg systems was found in patients with asthma. Foxp3 mRNA expression was decreased in asthma patients compared to healthy individuals. This could probably reflect an impaired regulatory role of Treg in asthma. At the same time, asthma severity was related to concentrations of Foxp3 mRNA and IL-17 and IL-6. This inverse relationship could indicate an imbalance between Foxp3+Treg and Th17 towards the increase in Th17 activity and the reduction in Foxp3+Treg cell number in asthma. Blood mononuclear cells of ABA patients were characterized by significantly increased expression of mRNA of c-Maf and GATA3 Th2-specific transcription factors, associated cytokines (IL-4, IL-13) and IgE. Nevertheless, ABA patients had lower T-bet expression compared to healthy individuals and NABA patients.

Conclusion. Asthma worsening in NABA patients was associated with reduced T-bet mRNA expression and increased GATA3 mRNA expression. This could be due to Th1/Th2-cell imbalance towards the increased Th2-response.

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