論文 - 詳細
| RRC ID | 78809 |
|---|---|
| 著者 | Okuma N, Ito MA, Shimizu T, Hasegawa A, Ohmori S, Yoshida K, Matsuoka I. |
| タイトル | Amplification of poly(I:C)-induced interleukin-6 production in human bronchial epithelial cells by priming with interferon-γ. |
| ジャーナル | Sci Rep |
| Abstract |
Proinflammatory cytokine interleukin (IL)-6 was associated with disease severity in patients with COVID-19. The mechanism underlying the excessive IL-6 production by SARS-Cov-2 infection remains unclear. Respiratory viruses initially infect nasal or bronchial epithelial cells that produce various inflammatory mediators. Here, we show that pretreatment of human bronchial epithelial cells (NCl-H292) with interferon (IFN)-γ (10 ng/mL) markedly increased IL-6 production induced by the toll-like receptor (TLR) 3 agonist poly(I:C) (1 µg/mL) from 0.4 ± 0.1 to 4.1 ± 0.4 ng/mL (n = 3, P < 0.01). A similar effect was observed in human alveolar A549 and primary bronchial epithelial cells. TLR3 knockdown using siRNA in NCl-H292 cells diminished the priming effects of IFN-γ on poly(I:C)-induced IL-6 production. Furthermore, the Janus kinase (JAK) inhibitor tofacitinib (1 µM) inhibited IFN-γ-induced upregulation of TLR3, and suppressed poly(I:C)-induced IL-6 production. Quantitative chromatin immunoprecipitation revealed that IFN-γ stimulated histone modifications at the IL-6 gene locus. Finally, IFN-γ priming significantly increased lung IL-6 mRNA and protein levels in poly(I:C)-administrated mice. Thus, priming bronchial epithelial cells with IFN-γ increases poly(I:C)-induced IL-6 production via JAK-dependent TLR3 upregulation and chromatin remodeling at the IL-6 gene locus. These mechanisms may be involved in severe respiratory inflammation following infection with RNA viruses. |
| 巻・号 | 13(1) |
| ページ | 21067 |
| 公開日 | 2023-11-29 |
| DOI | 10.1038/s41598-023-48422-9 |
| PII | 10.1038/s41598-023-48422-9 |
| PMID | 38030681 |
| PMC | PMC10687102 |
| MeSH | Animals Epithelial Cells / metabolism Humans Interferon-gamma* / metabolism Interleukin-6* / metabolism Interleukin-8 / metabolism Mice Poly I-C / pharmacology Toll-Like Receptor 3* / agonists |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549 |