Wågsäter Dick, Olofsson Peder S, Norgren Lars, Stenberg Björn, Sirsjö Allan
Division of Biomedicine, Department of Caring Sciences, University of Orebro, SE-701 82 Orebro, Sweden.
Biochem Biophys Res Commun. 2004 Dec 24;325(4):1187-93. doi: 10.1016/j.bbrc.2004.10.160.
Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-gamma, TNF-alpha, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-gamma was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-gamma induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL.
动脉粥样硬化是一种炎症性疾病,其特征在于趋化因子的参与,趋化因子对白细胞的募集很重要,还有介导泡沫细胞形成的清道夫受体。几种细胞因子参与动脉粥样硬化中趋化因子和清道夫受体的调节。CXCL16是一种趋化因子和清道夫受体,存在于人类动脉粥样硬化病变的巨噬细胞中。使用双标记免疫组织化学,我们发现人类病变中的平滑肌细胞表达CXCL16。然后我们分析了干扰素-γ、肿瘤坏死因子-α、白细胞介素-12、白细胞介素-15、白细胞介素-18和脂多糖对培养的主动脉平滑肌细胞中CXCL16表达的影响。干扰素-γ是最有效的CXCL16诱导剂,可增加CXCL16的信使核糖核酸、可溶性形式、膜形式和细胞总水平。干扰素-γ对CXCL16的诱导还与这些细胞对氧化型低密度脂蛋白摄取的增加有关。综上所述,平滑肌细胞在动脉粥样硬化病变中表达CXCL16,这可能在T细胞向动脉粥样硬化病变的吸引中起作用,并有助于修饰型低密度脂蛋白的细胞内化。