FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells
| Autor: | Michael D. Menger, Markus Bischoff, Frank Lammert, Frederik Seiler, Christian Herr, Andreas Kamyschnikow, Christoph Beisswenger, Jan Hellberg, Philipp M. Lepper, Robert Bals, Frank Langer, Hans-Joachim Schäfers |
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| Rok vydání: | 2013 |
| Předmět: |
Immunology
Antimicrobial peptides Respiratory Mucosa Biology Proinflammatory cytokine Mice Immunity Cell Line Tumor Tumor Cells Cultured medicine Animals Humans Immunology and Allergy Myeloid Cells Pseudomonas Infections Transcription factor Lung Innate immune system Forkhead Box Protein O3 fungi Forkhead Transcription Factors Immunity Innate Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Chronic Disease TLR3 hormones hormone substitutes and hormone antagonists Signal Transduction Respiratory tract |
| Zdroj: | The Journal of Immunology. 190:1603-1613 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1200596 |
| Popis: | Bacterial pathogens are a leading cause of lung infections and contribute to acute exacerbations in patients with chronic respiratory diseases. The innate immune system of the respiratory tract controls and prevents colonization of the lung with bacterial pathogens. Forkhead box transcription factor family O (FOXO) transcription factors are key regulators of cellular metabolism, proliferation, and stress resistance. In this study, our aim was to investigate the role of FOXO transcription factors in innate immune functions of respiratory epithelial cells. We show that bacterial pathogens potently activate FOXO transcription factors in cultured human respiratory epithelial cells in vitro. Infection of mice with bacterial pathogens resulted in the activation of FOXO transcription factors in alveolar and bronchial epithelial cells in vivo. Active FOXO was also detectable in human bronchial tissue obtained from subjects with different infection-related lung diseases. Small interfering RNA–mediated knockdown of FOXO in bronchial epithelial cells resulted in reduced expression of factors of the innate immune system such as antimicrobial peptides and proinflammatory cytokines, both under basal conditions and upon infection. FOXO deficiency further affected internalization of Haemophilus influenzae in bronchial epithelial cells. Finally, we show that TLR3 activates innate immune responses in a FOXO-dependent manner. In conclusion, FOXO transcription factors are involved in the cellular responses to bacterial stimuli and act as central regulators of innate immune functions in respiratory epithelial cells. |
| Databáze: | OpenAIRE |
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