We are analyzing https://link.springer.com/article/10.1186/1476-9255-2-14.

Title:
Differential signaling mechanisms regulate expression of CC chemokine receptor-2 during monocyte maturation | Journal of Inflammation
Description:
Background Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many chronic inflammatory pathologies of the vasculature including the formation of atherosclerotic lesions. However, the molecular and biochemical events underlying monocyte maturation are not fully understood. Methods We have used freshly isolated human monocytes and the model human monocyte cell line, THP-1, to investigate changes in the expression of a panel of monocyte and macrophage markers during monocyte differentiation. We have examined these changes by RT-PCR and FACS analysis. Furthermore, we cloned the CCR2 promoter and analyzed specific changes in transcriptional activation of CCR2 during monocyte maturation. Results The CC chemokine receptor 2 (CCR2) is rapidly downregulated as monocytes move down the macrophage differentiation pathway while other related chemokine receptors are not. Using a variety of biochemical and transcriptional analyses in the human THP-1 monocyte model system, we show that both monocytes and THP-1 cells express high levels of CCR2, whereas THP-1 derived macrophages fail to express detectable CCR2 mRNA or protein. We further demonstrate that multiple signaling pathways activated by IFN-γ and M-CSF, or by protein kinase C and cytoplasmic calcium can mediate the downregulation of CCR2 but not CCR1. Conclusion During monocyte-to-macrophage differentiation CCR2, but not CCR1, is downregulated and this regulation occurs at the level of transcription through upstream 5
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Keywords {🔍}

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Topics {✒️}

cxcr1-cxcr5 ccr4 chemokine receptors ccr1-ccr9 ccr1-ccr9 cxcr1-5 ccr7 temporarily increased ccr7 protein ccr7 mrna cxcr2 decreased ccr7 cxcr2 mrna cxcr4 mrnas cxcr2 cxcr4 c-fms proto-oncogene encodes human c-fms proto-oncogene tandem caat/enhancer-binding protein ccr5 [2 ccr5 broad-spectrum kinase inhibitor gapdh article download pdf g-protein coupled serpentine ccr1 remained high ifn-γ signals extensively myeloid-specific gene expression monocyte-derived macrophages express performed semi-quantitative analysis ice-cold staining buffer strand rt-pcr kit ccr2-/- mice reveals selective dose-dependent reduction ccr2-specific gene transcription ccr2-specific reporter construct authors’ original file broad-spectrum inhibitor dose-dependent selective downregulation lipid-laden foam cells peripheral blood monocytes signal transduction pathways coordinate cellular responses cellular adhesion assays selectively downregulate ccr2 binding sequence located privacy choices/manage cookies monocyte chemoattractant protein-1 molecular mechanisms underlying m-csf promotes specific ccr2 promoter-luciferase construct related subjects

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         headline:Differential signaling mechanisms regulate expression of CC chemokine receptor-2 during monocyte maturation
         description:Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many chronic inflammatory pathologies of the vasculature including the formation of atherosclerotic lesions. However, the molecular and biochemical events underlying monocyte maturation are not fully understood. We have used freshly isolated human monocytes and the model human monocyte cell line, THP-1, to investigate changes in the expression of a panel of monocyte and macrophage markers during monocyte differentiation. We have examined these changes by RT-PCR and FACS analysis. Furthermore, we cloned the CCR2 promoter and analyzed specific changes in transcriptional activation of CCR2 during monocyte maturation. The CC chemokine receptor 2 (CCR2) is rapidly downregulated as monocytes move down the macrophage differentiation pathway while other related chemokine receptors are not. Using a variety of biochemical and transcriptional analyses in the human THP-1 monocyte model system, we show that both monocytes and THP-1 cells express high levels of CCR2, whereas THP-1 derived macrophages fail to express detectable CCR2 mRNA or protein. We further demonstrate that multiple signaling pathways activated by IFN-γ and M-CSF, or by protein kinase C and cytoplasmic calcium can mediate the downregulation of CCR2 but not CCR1. During monocyte-to-macrophage differentiation CCR2, but not CCR1, is downregulated and this regulation occurs at the level of transcription through upstream 5' regulatory elements.
         datePublished:2005-10-31T00:00:00Z
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            Cellular Differentiation
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            Gene Regulation
            Immunology
            Allergology
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            Gastroenterology
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      headline:Differential signaling mechanisms regulate expression of CC chemokine receptor-2 during monocyte maturation
      description:Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many chronic inflammatory pathologies of the vasculature including the formation of atherosclerotic lesions. However, the molecular and biochemical events underlying monocyte maturation are not fully understood. We have used freshly isolated human monocytes and the model human monocyte cell line, THP-1, to investigate changes in the expression of a panel of monocyte and macrophage markers during monocyte differentiation. We have examined these changes by RT-PCR and FACS analysis. Furthermore, we cloned the CCR2 promoter and analyzed specific changes in transcriptional activation of CCR2 during monocyte maturation. The CC chemokine receptor 2 (CCR2) is rapidly downregulated as monocytes move down the macrophage differentiation pathway while other related chemokine receptors are not. Using a variety of biochemical and transcriptional analyses in the human THP-1 monocyte model system, we show that both monocytes and THP-1 cells express high levels of CCR2, whereas THP-1 derived macrophages fail to express detectable CCR2 mRNA or protein. We further demonstrate that multiple signaling pathways activated by IFN-γ and M-CSF, or by protein kinase C and cytoplasmic calcium can mediate the downregulation of CCR2 but not CCR1. During monocyte-to-macrophage differentiation CCR2, but not CCR1, is downregulated and this regulation occurs at the level of transcription through upstream 5' regulatory elements.
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      dateModified:2005-10-31T00:00:00Z
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         Cellular Differentiation
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         Allergology
         Cytokines and Growth Factors
         Rheumatology
         Pharmacology/Toxicology
         Gastroenterology
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