Role of STAT3 Transcription Factor in Pathogenesis of Bronchial Asthma

• Published in: Biochemistry (Moscow) 2021-11, Vol.86 (11), p.1489-1501
• Main Authors: Nikolskii, Aleksandr A., Shilovskiy, Igor P., Barvinskaia, Ekaterina D., Korneev, Artem V., Sundukova, Maria S., Khaitov, Musa R.
• Format: Article
• Language: English
• Subjects: Allergens; Animals; Asthma; Asthma - immunology; Asthma - pathology; B cells; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell activation; Chemokines; Cytokines; DNA binding proteins; Endothelial cells; Eosinophils; External stimuli; Genetic aspects; Helper cells; Humans; Hyperreactivity; Hypersensitivity; Inflammation; Inflammatory diseases; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Leukocytes - immunology; Leukocytes - pathology; Life Sciences; Lung - immunology; Lung - pathology; Lungs; Lymphocytes B; Lymphocytes T; Macrophages; Medical research; Medicine, Experimental; Microbiology; Neutrophils; Pathogenesis; Pollutants; Respiratory tract; Review; Signs and symptoms; Stat3 protein; STAT3 Transcription Factor - immunology; Therapeutic targets; Transcription factors
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297921110122

Bronchial asthma is a heterogeneous chronic inflammatory disease of airways. The studies of molecular and cellular mechanisms of bronchial asthma have established that a wide range of immune (T and B cells, eosinophils, neutrophils, macrophages, etc.) and structural (epithelial and endothelial) cells are involved in its pathogenesis. These cells are activated in response to external stimuli (bacteria, viruses, allergens, and other pollutants) and produce pro-inflammatory factors (cytokines, chemokines, metalloproteinases, etc.), which ultimately leads to the initiation of pathological processes in the lungs. Genes encoding transcription factors of the STAT family (signal transducer and activator of transcription), that includes seven representatives, are involved in the cell activation. Recent studies have shown that the transcription factor STAT3 plays an important role in the activation of the abovementioned cells, thus contributing to the development of asthma. In animal studies, selective inhibition of STAT3 significantly reduces the severity of lung inflammation, which indicates its potential as a therapeutic target. In this review, we describe the mechanisms of STAT3 activation and its role in polarization of Th2/Th17 cells and M2 macrophages, as well as in the dysfunction of endothelial cells, which ultimately leads to development of bronchial asthma symptoms, such as infiltration of neutrophils and eosinophils into the lungs, bronchial hyperreactivity, and the respiratory tract remodeling.