Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
Exp Mol Pathol. 2014 Apr;96(2):133-8. doi: 10.1016/j.yexmp.2014.01.002. Epub 2014 Jan 24.
Chemokines act as important secondary inflammatory mediators which are released by cells in response to a variety of stimuli. Chemokines bind to cell surface receptors and act as second-order cytokines with specialized functions in inflammation. The role of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) (also called CCL5 (chemokine (C-C motif) ligand 5)) has received little attention to date in disc tissue. Microarray analyses of lumbar disc annulus tissue revealed that RANTES expression was significantly upregulated in more degenerated Thompson grades IV and V discs compared to expression levels in grades I, II and III discs (p=0.032). Immunolocalization confirmed the presence of RANTES in the annulus and nucleus of the disc, and localized the RANTES receptors CCR1, CCR3 and CCR5 to cells in the disc. In vitro studies with IL-1-β and TNF-α challenges, both proinflammatory cytokines resulted in elevated levels of RANTES in conditioned media (p<0.01); TNF-α exposure, however, produced significantly greater levels than did IL-1alpha (p<0.0001), suggesting a differential regulation by TNF-α. Local production of RANTES in vivo by annulus and nucleus cells, and in vitro induction of RANTES by proinflammatory cytokines suggest that disc cells are primary effector cells as well as target cells, and thus can mediate physiological immune-related processes during disc degeneration by both autocrine and paracrine signaling.
趋化因子作为重要的次级炎症介质，可在细胞受到各种刺激时被释放。趋化因子与细胞表面受体结合，作为二级细胞因子发挥作用，具有在炎症中发挥特殊功能的专业化特性。RANTES（激活后正常 T 细胞表达和分泌）（也称为 CCL5（趋化因子（C-C 基序）配体 5））在椎间盘组织中的作用迄今为止尚未得到充分关注。对腰椎间盘环组织的微阵列分析显示，RANTES 的表达在更退变的 Thompson 分级 IV 和 V 椎间盘组织中明显上调，与 I、II 和 III 级椎间盘组织中的表达水平相比（p=0.032）。免疫组化定位证实 RANTES 存在于椎间盘的环和核中，并且 RANTES 受体 CCR1、CCR3 和 CCR5 定位于椎间盘细胞。体外用 IL-1-β 和 TNF-α 进行的研究表明，这两种促炎细胞因子均可导致条件培养基中 RANTES 水平升高（p<0.01）；然而，TNF-α 的暴露比 IL-1α 产生的水平显著更高（p<0.0001），这表明 TNF-α 的调节作用存在差异。环和核细胞在体内局部产生 RANTES，促炎细胞因子在体外诱导 RANTES 产生，这表明椎间盘细胞既是主要的效应细胞也是靶细胞，因此可以通过自分泌和旁分泌信号传导，在椎间盘退变过程中调节与生理免疫相关的过程。
