Genistein Attenuated Allergic Airway Inflammation by Modulating the Transcription Factors T-bet, GATA-3 and STAT-6 in a Murine Model of Asthma

• Published in: Pharmacology Vol. 89; no. 3-4; pp. 229 - 236
• Main Authors: Gao, Fei, Wei, Dong, Bian, Tao, Xie, Ping, Zou, Jian, Mu, Huijun, Zhang, Bin, Zhou, Xiaoyan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2012
• Subjects: Allergens - immunology; Allergies; Animals; Anti-Allergic Agents - therapeutic use; Anti-Inflammatory Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - pathology; Bronchoalveolar Lavage Fluid - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cells, Cultured; Cytokines; Cytokines - blood; Cytokines - immunology; Disease Models, Animal; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - immunology; Gene expression; Genistein - therapeutic use; Male; Mice; Mice, Inbred BALB C; Original Paper; Ovalbumin - immunology; Phytochemicals; RNA, Messenger - immunology; Rodents; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - immunology; T-Box Domain Proteins - genetics; T-Box Domain Proteins - immunology; Transcription factor; Genistein; Cytokine; Asthma
• ISSN: 0031-7012; 1423-0313; 1423-0313
• DOI: 10.1159/000337180

Background: Genistein, a flavonoid in legumes and some herbal medicines, has various biological actions. Previous studies have shown that genistein decreased airway inflammation in allergic asthma. However, studies on how genistein affects immunoreactions in asthma are very limited. Objective: It was the aim of this study to investigate the effect of genistein on T helper 1 (Th1)/Th2 cytokines in a murine asthma model and to explore its underlying mechanisms. Methods: The asthma model was set up both in vivo and in vitro: the mice were divided into four groups in vivo, i.e. control group, ovalbumin-sensitized (OVA) group, Gen20 group (20 mg/kg genistein) and Gen40 group (40 mg/kg genistein), and into three groups in vitro, i.e. control group, OVA group, genistein group. Changes in lung histology were observed and concentrations of interleukin-4, interleukin-5 and interferon-γ in bronchoalveolar lavage fluid and serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of GATA binding protein 3 (GATA-3), signal transducer and activator of transcription 6 (STAT-6) and T-box transcription factor (T-bet) in the lungs and CD4+ T cells of each group were detected by real-time PCR and the corresponding proteins were detected by Western blot. Results: The results showed that genistein attenuated OVA-induced airway inflammation, decreased Th2-type cytokines and increased Th1-type cytokines. Additionally, our data suggested that genistein may modulate the Th1/Th2 reaction by inhibiting GATA-3 and STAT-6 production while increasing T-bet production. Conclusion: Genistein may modulate the immunomodulatory actions caused by Th1/Th2 cytokines in asthma, at least partially, by the down-regulation of GATA-3 and STAT-6 and the up-regulation of T-bet.