Dose-Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages.
Dose-Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages.
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声带成纤维细胞和巨噬细胞转录因子的剂量依赖性糖皮质激素调节。
DOI：
10.1002/lary.30594
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Branski,RyanC
中科院分区：
文献类型：
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作者：
Nakamura,Ryosuke;Bing,Renjie;Gartling,GaryJ;Garabedian,MichaelJ;Branski,RyanC
目的糖皮质激素（GC）治疗喉部疾病的不同结果被认为是由于GC受体（GR）与细胞信号通路的不同相互作用，对浓度依赖效应的考虑有限，以及GC的选择不一致。在本研究中，我们评估了三种常用的GCs对转录因子的浓度依赖性影响，重点研究了GR的Ser203和Ser211的磷酸化调节GR的核易位。本研究为GCs的不同功能提供了基础数据，以优化治疗方法。研究设计体外实验。方法用不同浓度的地塞米松、甲基强的松龙和曲安奈德联合IFN‐γ、TNF‐α或il - 4治疗人声襞成纤维细胞和THP1‐来源的巨噬细胞。Western blotting分析磷酸化STAT1、NF - κB家族分子和磷酸化STAT6。我们还分析了Ser211‐磷酸化GR （S211‐pGR）相对于GAPDH和Ser203‐磷酸化GR （S203‐pGR）的水平。结果在IFN - γ和TNF - α刺激下，gcs可改变不同细胞类型的STAT1和NF - κB家族磷酸化分子。在il - 4处理的巨噬细胞中，GCs没有改变磷酸化的STAT6。三种GCs几乎相等。无论细胞类型和处理方式如何，较低浓度的地塞米松增加了S211‐pGR/GAPDH比值，而增加了S211‐pGR/S203‐pGR比值。结论三种GCs对两种细胞系的转录因子调控作用基本相同。在低GC浓度下，相对高水平的Ser203‐磷酸化可能与两种细胞系中GC的浓度依赖性差异效应有关。证据水平[j] .中华耳鼻喉杂志，33 (3):2704 - 2711,2023
ObjectiveVariable outcomes of glucocorticoid (GC) therapy for laryngeal disease are putatively due to diverse interactions of the GC receptor (GR) with cell signaling pathways, limited consideration regarding concentration‐dependent effects, and inconsistent selection of GCs. In the current study, we evaluated the concentration‐dependent effects of three frequently administered GCs on transcription factors with an emphasis on the phosphorylation of GR at Ser203 and Ser211 regulating the nuclear translocation of GR. This study provides foundational data regarding the diverse functions of GCs to optimize therapeutic approaches.Study designIn vitro.MethodsHuman vocal fold fibroblasts and THP1‐derived macrophages were treated with different concentrations of dexamethasone, methylprednisolone, and triamcinolone in combination with IFN‐γ, TNF‐α, or IL4. Phosphorylated STAT1, NF‐κB family molecules, and phosphorylated STAT6 were analyzed by Western blotting. Ser211‐phosphorylated GR (S211‐pGR) levels relative to GAPDH and Ser203‐phosphorylated GR (S203‐pGR) were also analyzed.ResultsGCs differentially altered phosphorylated STAT1 and NF‐κB family molecules in different cell types under IFN‐γ and TNF‐α stimuli. GCs did not alter phosphorylated STAT6 in IL4‐treated macrophages. The three GCs were nearly equivalent. A lower concentration of dexamethasone increased S211‐pGR/GAPDH ratios relative to increased S211‐pGR/S203‐pGR ratios regardless of cell type and treatment.ConclusionThe three GCs employed in two cell lines had nearly equivalent effects on transcription factor regulation. Relatively high levels of Ser203‐phosphorylation at low GC concentrations may be related to concentration‐dependent differential effects of GCs in the two cell lines.Level of EvidenceNALaryngoscope, 133:2704–2711, 2023