Sato K, Kawasaki H, Nagayama H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Takahashi T A
Department of Cell Processing, AIDS Research Center, Institute of Medical Science, University of Tokyo, Japan.
J Immunol. 2000 Mar 1;164(5):2285-95. doi: 10.4049/jimmunol.164.5.2285.
We examined the effect of TGF-beta 1 on the chemotactic migratory ability of human monocyte-derived dendritic cells (DCs). Treatment of immature DCs with TGF-beta 1 resulted in increased expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXC chemokine receptor-4 (CXCR-4), which were concomitant with enhanced chemotactic migratory responses to their ligands, RANTES (for CCR-1, CCR-3, and CCR-5), macrophage-inflammatory protein-3 alpha (MIP-3 alpha) (for CCR-6), or stromal cell-derived growth factor-1 alpha (for CXCR-4). Ligation by TNF-alpha resulted in down-modulation of cell surface expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and the chemotaxis for RANTES, MIP-3 alpha, and stromal cell-derived growth factor-1 alpha, whereas this stimulation up-regulated the expression of CCR-7 and the chemotactic ability for MIP-3beta. Stimulation of mature DCs with TGF-beta 1 also enhanced TNF-alpha-induced down-regulation of the expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and chemotaxis to their respective ligands, while this stimulation suppressed TNF-alpha-induced expression of CCR-7 and chemotactic migratory ability to MIP-3 beta. Our findings suggest that TGF-beta 1 reversibly regulates chemotaxis of DCs via regulation of chemokine receptor expression.
我们研究了转化生长因子β1（TGF-β1）对人单核细胞来源的树突状细胞（DCs）趋化迁移能力的影响。用TGF-β1处理未成熟DCs导致CCR-1、CCR-3、CCR-5、CCR-6和CXC趋化因子受体4（CXCR-4）的表达增加，这与对其配体RANTES（针对CCR-1、CCR-3和CCR-5）、巨噬细胞炎性蛋白-3α（MIP-3α）（针对CCR-6）或基质细胞衍生生长因子-1α（针对CXCR-4）的趋化迁移反应增强相伴。肿瘤坏死因子-α（TNF-α）的结合导致CCR-1、CCR-3、CCR-5、CCR-6和CXCR-4的细胞表面表达下调，以及对RANTES、MIP-3α和基质细胞衍生生长因子-1α的趋化性降低，而这种刺激上调了CCR-7的表达和对MIP-3β的趋化能力。用TGF-β1刺激成熟DCs也增强了TNF-α诱导的CCR-1、CCR-3、CCR-5、CCR-6和CXCR-4表达下调以及对其各自配体的趋化性，同时这种刺激抑制了TNF-α诱导的CCR-7表达和对MIP-3β的趋化迁移能力。我们的研究结果表明，TGF-β1通过调节趋化因子受体表达可逆地调节DCs的趋化性。
