Fractalkine/CX3CL1 production by human airway smooth muscle cells:: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids
Fractalkine/CX3CL1 production by human airway smooth muscle cells:: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids
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DOI：
10.1152/ajplung.00014.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Chung, KF
中科院分区：
文献类型：
--
作者：
Sukkar, MB;Issa, R;Chung, KF
气道平滑肌细胞（ASMC）合成趋化因子可能是哮喘和慢性阻塞性肺疾病（COPD）等气道炎症性疾病中炎症细胞募集的重要过程。Fractalkine（FKN）是最近描述的CX 3C趋化因子，其具有双重功能，作为细胞粘附分子和单核细胞和T细胞的化学引诱物，表达其独特的受体CX（3）CR 1。我们研究了人ASMC对促炎细胞因子IL-1 β、TNF-α和IFN-γ，T辅助细胞2型细胞因子IL-4、IL-10和IL-13，以及纤维化细胞因子转化生长因子（TGF）-β的反应中FKN的表达。这些细胞因子单独对ASMC FKN的产生没有任何显著影响。IFN-γ和TNF-α的联合刺激以时间和浓度依赖性方式诱导FKN mRNA和蛋白表达。TGF-β具有显著的抑制作用，马槟榔诱导的FKN的mRNA和蛋白质的表达。地塞米松（10（-8）-10（-6）M）显著上调马槟榔诱导的FKN mRNA和蛋白表达。最后，我们使用了丝裂原活化蛋白激酶c-Jun NH 2-末端激酶（JNK）（SP-610025）、p38（SB-203580）和细胞外信号调节激酶（PD-98095）的选择性抑制剂来研究它们在FKN产生中的作用。SP-610025（25 μ M）和SB-203580（20 μ M），但PD-98095，显着减弱奎宁诱导的FKN蛋白质合成。IFN-γ和TNF-α诱导的JNK磷酸化在TGF-β存在下保持不变，但被地塞米松抑制，表明JNK不参与TGF-β或地塞米松介导的FKN产生调节。总之，体外人ASMC的FKN产生受炎症和抗炎因子调节。
Chemokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX(3)CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-beta. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-gamma and TNF-alpha induced FKN mRNA and protein expression in a time- and concentration-dependent manner. TGF-beta had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10(-8)-10(-6) M) significantly upregulated cytokine-induced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 muM) and SB-203580 (20 muM), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-gamma- and TNF-alpha-induced JNK phosphorylation remained unaltered in the presence of TGF-beta but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-beta- or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors.