地塞米松和福莫特罗对THP-1细胞分化的巨噬细胞表面TLR4表达的影响

Effect of dexamethasone and formoterol on expression of TLR4 in macrophages differentiated fromTHP-1 cell line

目的通过体外实验测定地塞米松和福莫特罗对人单核细胞系（THP一1）分化的巨噬细胞表面Toll样受体4（TLR4）表达的影响。方法用不同浓度地塞米松和（或）福莫特罗刺激THP．1细胞系分化的巨噬细胞，采用逆转录-聚合酶链反应（RT—PCR）和蛋白质印迹法（Westernblotting）测定细胞在有或没有脂多糖刺激时TLR4mRNA和蛋白表达水平。结果脂多糖浓度依赖性上调TLR4mRNA和蛋白表达水平。单用地塞米松（10^-10～10^-6mol／L）下调TLR4表达，单用福莫特罗（10^-7和10^-6moL／L）上调TLR4水平。联合刺激时，福莫特罗（10^-6mol／L）能部分逆转地塞米松（10^6mol／L）对TLR4表达的下调作用。结论福莫特罗和（或）地塞米松对TLR4的影响可能是联合作用的机制之一，对治疗革兰阴性细菌引起的气道炎症有重要意义。

Objective Inhaled corticosteroids combined with long β2-adrenoceptor agonist are widely used in treatment of chronic obstructive pulmonary disease, but mechanisms remain unclear. Meth- ods Macrophage cells differentiated from THP-1 cell line were stimulated with dexamethasone and/or for- moterol with or without lipopolysaccharide （LPS）. TLR4 mRNA and protein were examined by reverse tran- scriptase polymerase chain reaction （RT-PCR） and Western blotting. Results A dose-dependent up regu- lation in TLR4 mRNA and protein expression in the presence of LPS was found. Treatment with dexametha- sone （ 10^-10 10^-6mol/L） resulted in a dose-dependent reduction in TLR4 mRNA and protein. Stimulation with formeterol （10^-7 mol/L and 10-6 mol/L） caused up regulation of TLR4. Formoterol （10^-6 mol/L） partially reversed the inhibitory effect of dexamethasone （ 10 ^-6 mol/L） on TLR4 expression in the presence of LPS. Conclusions Modulation of TLR4 in macrophages by dexamethasone and/or formoterol may be one of the mechanisms for combination and have important implications for the treatment of airway inflammation in response to gram-negative bacteria.