TGFβ1 selectively up-regulates CCR1 expression in primary murine astrocytes

Abstract

Chemokine receptors dictate the cellular responses to chemokines on target cells. Therefore, the regulation of expression of chemokine receptors is likely a crucial point for the regulation of chemokine action. Here we show that CC chemokine receptor 1 (CCR1) expression by primary mouse astrocytes is increased after transforming growth factor beta1 (TGFbeta1) stimulation. TGFbeta1 caused a pronounced up-regulation of CCR1 mRNA in a concentration- and time-dependent manner. TGFbeta1-mediated increase of CCR1 mRNA accumulation resulted in increased CCR1 protein expression and augmented cell migration to a physiological ligand, macrophage inflammatory protein-1alpha (MIP-1alpha). The half life of CCR1 mRNA in the presence and absence of TGFbeta1 stimulation was comparable, suggesting that TGFbeta1-induced CCR1 mRNA accumulation occurred at the transcriptional level. TGFbeta1 did not affect CCR1 mRNA expression in hematopoietic cells, indicating that TGFbeta1 effect on CCR1 expression in primary astrocytes is cell-type specific. This is the first evidence that TGFbeta1 may modulate central nervous system (CNS) inflammation in part by affecting chemokine receptor expression on astrocytes.

Negative role of cAMP‐dependent protein kinase A in RANTES‐mediated transcription of proinflammatory mediators through Raf

“…Our previous studies demonstrated that stimulation of primary neonatal mouse astrocytes with 1-10 nM RANTES induced chemokine and cytokine transcription, including de novo induction of mRNA for KC, RANTES, MIP-1α, MIP-2, MCP-1, TNF-α, and IL-6 (6,8). Astrocytes were shown to express two high affinity RANTES receptors, CCR1 (CC chemokine receptor 1) and CCR5 (5,6,24). These seven-transmembrane spanning G protein-coupled receptors are often coupled to G proteins that modulate adenylyl cyclase activity (9).…”

The chemokine receptor CCR1 is strongly up‐regulated after skin injury but dispensable for wound healing

“…Other names for the receptor are CC CKR1, HM145, MIP‐1α/R, 12 CMKBR1, 13 LD78 receptor, 14 and MIP‐1α/RANTES R 9 . Since its isolation, CCR1 expression has been reported on several different cell types, e.g., B cells, T cells, neutrophils, monocytes, eosinophils, platelets, and astrocytes 9,10 , 15–18 . So far, eight chemokines have been identified as CCR1 agonists: macrophage inflammatory protein 1α (MIP‐1α/CCL3), regulated on activation of normal T cell expressed and secreted (RANTES/CCL5), monocyte chemoattractant protein 3 (MCP‐3/CCL7), hemofiltrate CC chemokines 1, 2, and 4 (HCC‐1/CCL14; HCC‐2/CCL15; HCC‐4/CCL16), myeloid progenitor inhibitory factor 1 (MPIF‐1/CCL23) (reviewed in 12 ), and monocyte chemoattractant protein 2 (MCP‐2/CCL8) 19 …”

CNS-specific expression of C3a and C5a exacerbate demyelination severity in the cuprizone model

“…Microglia have previously been shown to express CCR3 and CCR5, receptors for CCL4 and CCL5 (Albright et al, 1999). Astrocytes also express CCR3, in addition to CCR1, another receptor for CCL5 (Flynn et al, 2003; Han et al, 2000). Additionally, previous cuprizone studies have shown that chemokine mRNA transcripts are upregulated in the brain during cuprizone treatment; including, CCL4 and CCL5 (Biancotti et al, 2008; McMahon et al, 2001).…”