1. IL-27 regulates IL-4-induced chemokine production in human bronchial epithelial cells.
- Author
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Pereira ABM, de Oliveira JR, Teixeira MM, da Silva PR, Rodrigues Junior V, and Rogerio AP
- Subjects
- Cell Movement, Chemokines metabolism, Gene Expression Regulation, Humans, Interleukin-27 genetics, Interleukin-4 metabolism, Molecular Targeted Therapy, NF-kappa B metabolism, STAT6 Transcription Factor metabolism, Bronchi pathology, Epithelial Cells physiology, Immune System Diseases immunology, Inflammation immunology, Interleukin-27 metabolism, Th1 Cells immunology, Th2 Cells immunology
- Abstract
IL-4 coordinates the Th2-type immune response in inflammatory diseases such as asthma. IL-27 can inhibit the development of both Th2 and Th1 cells. However, IL-27 can also drive naïve T cells to differentiate toward the Th1 phenotype. In this study, we investigated the effects of IL-27 on the activation of IL-4-induced human bronchial epithelial cells (BEAS-2B). Compared to controls, both IL-4 and IL-27 (25-100 ng/mL) increased the concentrations of CCL2 and IL-8 in a dose-dependent manner. However, compared to cells stimulated individually with IL-4 or IL-27, treatment with a combination of both cytokines reduced CCL2 and IL-8 concentrations in a dose- and time-dependent manner. IL-4 increased the activation of p38 MAPK, ERK1/2, STAT6 and NF-κB, while IL-27 increased the activation of p38 MAPK and ERK1/2 but not STAT6 and NF-κB. Compared to IL-4-stimulated cells, cells treated with both IL-27 and IL-4 displayed decreased activation of STAT6 and NF-κB but not ERK1/2 and p38 MAPK. Taken together, these results suggest that IL-27 plays a pro-inflammatory role when administered alone but downregulates bronchial epithelial cell activation when combined with IL-4. Therefore, IL-27 may be an interesting target for the treatment of Th2 inflammatory diseases., (Copyright © 2020 Elsevier GmbH. All rights reserved.)
- Published
- 2021
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