Sica A, Saccani A, Borsatti A, Power C A, Wells T N, Luini W, Polentarutti N, Sozzani S, Mantovani A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Exp Med. 1997 Mar 3;185(5):969-74. doi: 10.1084/jem.185.5.969.
The present study was designed to investigate the effect of bacterial lipopolysaccharide (LPS) on C-C chemokine receptors (CCR) expressed in human mononuclear phagocytes. LPS caused a rapid and drastic reduction of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs were also reduced, though to a lesser extent, whereas CXCR2 was unaffected. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced from 1.5 h to 45 min. As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness. The capacity to inhibit CCR2 expression in monocytes was shared by other microbial agents and cytokines (inactivated Streptococci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF-alpha). In contrast, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. These results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of the chemokine system.
本研究旨在探讨细菌脂多糖（LPS）对人单核吞噬细胞中表达的C-C趋化因子受体（CCR）的影响。LPS导致与单核细胞趋化蛋白-1（MCP-1）和单核细胞趋化蛋白-3结合的CCR2 mRNA水平迅速大幅降低。CCR1和CCR5 mRNA也有所降低，不过降低程度较小，而CXC趋化因子受体2（CXCR2）则未受影响。CCR2的核转录速率不受LPS影响，但其mRNA半衰期从1.5小时缩短至45分钟。正如预期的那样，LPS诱导的CCR2 mRNA表达抑制与MCP-1结合及趋化反应性的降低相关。其他微生物因子和细胞因子（灭活的链球菌、痤疮丙酸杆菌，以及程度较轻的白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α））也具有抑制单核细胞中CCR2表达的能力。相比之下，IL-2可增强CCR2表达，而MCP-1本身则无影响。这些结果表明，除了激动剂产生外，受体表达的调节可能是趋化因子系统调节中的一个关键点。
