Interferon-λ1 improves glucocorticoid resistance caused by respiratory syncytial virus by regulating the p38 mitogen-activated protein kinase signaling pathway.
10.7499/j.issn.1008-8830.2501095
- Author:
Li PENG
1
;
Yao LIU
1
;
Fang-Cai LI
;
Xiao-Fang DING
1
;
Xiao-Juan LIN
1
;
Tu-Hong YANG
1
;
Li-Li ZHONG
1
Author Information
1. Children's Medical Center, Hunan Provincial People's Hospital/First Affiliated Hospital of Hunan Normal University/Hunan Key Laboratory of Pediatric Respiratory Diseases, Changsha 410005, China.
- Publication Type:Journal Article
- Keywords:
Glucocorticoid resistance;
Human bronchial epithelial cell;
Interferon-λ1;
Respiratory syncytial virus;
p38 mitogen-activated protein kinase
- MeSH:
Humans;
p38 Mitogen-Activated Protein Kinases/genetics*;
Glucocorticoids/pharmacology*;
Receptors, Glucocorticoid/analysis*;
Dual Specificity Phosphatase 1/physiology*;
Dexamethasone/pharmacology*;
Drug Resistance/drug effects*;
Respiratory Syncytial Viruses;
Interferons/pharmacology*;
MAP Kinase Signaling System/drug effects*;
Epithelial Cells/drug effects*;
Signal Transduction/drug effects*;
Cells, Cultured
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(8):1011-1016
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV).
METHODS:HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated.
RESULTS:At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05).
CONCLUSIONS:IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
