| RRC ID |
78809
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| 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
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| DOI |
10.1038/s41598-023-48422-9
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| 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
|
| リソース情報 |
| ヒト・動物細胞 |
A549 |
