Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists
Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists
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DOI：
10.3389/fphys.2019.01267
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发表时间：
2019-10-02
影响因子：
4
通讯作者：
Devillier, Philippe
中科院分区：
文献类型：
--
作者：
Grassin-Delyle, Stanislas;Salvator, Helene;Devillier, Philippe
背景：苦味受体（TAS 2 R）参与气道舒张，但也在人血白细胞中表达。我们研究了TAS 2 R的表达和TAS 2 R激动剂对脂多糖（LPS）诱导的人肺巨噬细胞（LMs）中细胞因子释放的影响。我们使用RT-qPCR测量未刺激和LPS刺激（10 ng.mL（-1））LM中16种TAS 2 R（TAS 2 R 3/4/5/7/8/9/10/14/19/20/31/38/39/43/45和46）的转录物。巨噬细胞还与TAS 2 R激动剂一起孵育24小时。结果：16种TAS 2 R基因在巨噬细胞中均有表达。LPS的加入导致大多数TAS 2 R的表达增加，这对于TAS 2 R7和38是显著的。尽管混杂的TAS 2 R激动剂奎宁和地那铵抑制了LPS诱导的TNF-α、CCL 3和CXCL 8的释放，但地芬尼多无活性。部分选择性激动剂（氨苯砜、秋水仙碱、士的宁和氯喹）和选择性激动剂[红霉素（TAS 2 R10）、菲咯啉（TAS 2 R5）、氧氟沙星（TAS 2 R9）和卡立普多（TAS 2 R14）]也抑制LPS诱导的细胞因子释放。相反，另外两种激动剂[色甘酸钠（TAS 2 R20）和糖精（TAS 2 R31和43）]无活性。TAS 2 R激动剂抑制IL-10的生产-这表明，这种抗炎细胞因子是不参与抑制细胞因子production.Conclusion：人类LM表达TAS 2 Rs。使用TAS 2 R激动剂的实验表明TAS 2 R 3、4、5、9、10、14、30、39和40参与细胞因子产生的抑制。TAS 2 Rs可能成为炎症性阻塞性肺疾病的新药物靶点。
Background: Bitter-taste receptors (TAS2Rs) are involved in airway relaxation but are also expressed in human blood leukocytes. We studied TAS2R expression and the effects of TAS2R agonists on the lipopolysaccharide (LPS)-induced cytokine release in human lung macrophages (LMs).Methods: Lung macrophages were isolated from patients undergoing surgery for carcinoma. We used RT-qPCR to measure transcripts of 16 TAS2Rs (TAS2Rs 3/4/5/7/8/9/10/14/19/20/31/38/39/43/45 and 46) in unstimulated and LPS-stimulated (10 ng.mL(-1)) LMs. The macrophages were also incubated with TAS2R agonists for 24 h. Supernatant levels of the cytokines TNF-alpha, CCL3, CXCL8 and IL-10 were measured using ELISAs.Results: The transcripts of all 16 TAS2Rs were detected in macrophages. The addition of LPS led to an increase in the expression of most TAS2Rs, which was significant for TAS2R7 and 38. Although the promiscuous TAS2R agonists, quinine and denatonium, inhibited the LPS-induced release of TNF-alpha, CCL3 and CXCL8, diphenidol was inactive. Partially selective agonists (dapsone, colchicine, strychnine, and chloroquine) and selective agonists [erythromycin (TAS2R10), phenanthroline (TAS2R5), ofloxacin (TAS2R9), and carisoprodol (TAS2R14)] also suppressed the LPS-induced cytokine release. In contrast, two other agonists [sodium cromoglycate (TAS2R20) and saccharin (TAS2R31 and 43)] were inactive. TAS2R agonists suppressed IL-10 production - suggesting that this anti-inflammatory cytokine is not involved in the inhibition of cytokine production.Conclusion: Human LMs expressed TAS2Rs. Experiments with TAS2R agonists' suggested the involvement of TAS2Rs 3, 4, 5, 9, 10, 14, 30, 39 and 40 in the inhibition of cytokine production. TAS2Rs may constitute new drug targets in inflammatory obstructive lung disease.