Abstract
The chemokine receptor CCR5 regulates trafficking of immune cells of the lymphoid and the myeloid lineage (such as monocytes, macrophages and immature dendritic cells) and microglia. Because of this, there is an increasing recognition of the important role of CCR5 in the pathology of (neuro-) inflammatory diseases such as atherosclerosis and multiple sclerosis. Expression of CCR5 is under the control of a complexly organized promoter region upstream of the gene. The transcription factor cAMP-responsive element binding protein 1 (CREB-1) transactivates the CCR5 P1 promoter. The cell-specific expression of CCR5 however is realized by using various epigenetic marks providing a multivalent chromatin state particularly in monocytes. Here we discuss the transcriptional regulation of CCR5 with a focus on the epigenetic peculiarities of CCR5 transcription.
Highlights
IntroductionsCC chemokine receptor 5 (CCR5), a receptor for the CC chemokines macrophage inflammatory protein-Į (MIP-1Į), macrophage inflammatory protein-ȕ (MIP-1ȕ), and regulated and normal T cell expressed and secreted (RANTES), regulates trafficking of lymphoid cells such as memory/effector
The chemokine receptor chemokine receptor 5 (CCR5) regulates trafficking of immune cells of the lymphoid and the myeloid lineage and microglia
CCR5 is implicated in the pathogenesis of various inflammatory diseases such as atherosclerosis and multiple sclerosis [4±7]
Summary
CC chemokine receptor 5 (CCR5), a receptor for the CC chemokines macrophage inflammatory protein-Į (MIP-1Į), macrophage inflammatory protein-ȕ (MIP-1ȕ), and regulated and normal T cell expressed and secreted (RANTES), regulates trafficking of lymphoid cells such as memory/effector. CCR5 is implicated in the pathogenesis of various inflammatory diseases such as atherosclerosis and multiple sclerosis [4±7]. Circulating monocytes are attracted to inflammatory sites by chemokine receptors, where they can differentiate into e.g., macrophages or microglia [22±24]. Atherosclerosis and multiple sclerosis are greatly characterized by inflammatory lesions, consisting of T cells and macrophages or microglia, respectively [25±27]. The chemokine receptor CCR5 is implicated in the pathogenesis of both of these diseases [8,9,28,29]. With CCR5 being implicated in various (inflammatory) diseases and as co-receptor for HIV-1 infection, much work has been put into the transcriptional regulation of CCR5. CREB-1, have been shown to play a role in CCR5 transcriptional regulation, its cell type specific expression is controlled by epigenetic mechanisms. In this review we will discuss the regulation of CCR5 expression, with the focus on epigenetic regulation and the possible pharmacological intervention in these epigenetic regulatory processes
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