Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus

Mine, Shinichiro; Okada, Yosuke; Tanikawa, Takahisa; Kawahara, Chie; Tabata, Toshiharu; Tanaka, Yoshiya

doi:10.1016/j.bbrc.2006.03.197

Cited by 67 publications

(46 citation statements)

References 25 publications

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“…Epidemiological studies revealed controversial results for a correlation of fasting glucose and MCP-1 levels in type 1 and 2 diabetic patients. This controversy might be due to the influence of blood glucose on MCP-1 production in several cell types and differential glycaemic control in diabetic patients (47,48). In this study, a trend for differences in fasting glucose was found for the different genotypes of c.-928GOC.…”

Section: Metabolic Syndrome and Parameters From Idf Definitionmentioning

confidence: 49%

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Sedlmeier¹,

Grallert²,

Huth³

et al. 2007

eur j endocrinol

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Objective: Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the development of several components of metabolic syndrome (MetS). The present study investigated the association of nine MCP-1 single nucleotide polymorphisms (SNPs) with MetS, type 2 diabetes mellitus and metabolic risk factors. Subjects and methods: The population-based study sample comprised 1630 subjects aged 55-74 years from KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4). Genotyping was carried out by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis of alleledependent primer extension products. Results: The MCP-1 SNP c.-3813COT exhibited trends for differences between the genotype groups in triglycerides, 2-h glucose and uric acid (PZ0.0084, 0.014, 0.027). Other trends were observed for c.-928GOC associated with height and fasting glucose (PZ0.0024, 0.033), for c.105TOC with height and leukocytes (PZ0.0095, 0.047), for c.*65COT and c.*3879COT with MCP-1 levels (both PZ0.012) and for c.-2138AOT with interleukin-6 levels. After correction for multiple testing, none of the analysed SNPs, except c.-928GOC in men showed a significant association with MetS, T2DM or other analysed parameters. Haplotype MCP-1*1 and c.-928GOC in men (PZ0.0002, 0.0004) were significantly associated with an increase in height. Conclusions: This is the first study to investigate the associations of MCP-1 SNPs with MetS. We found trends for several components of MetS. These parameters were hyperlipidaemia, fasting and 2-h glucose, and uric acid. A new finding is that MCP-1*1 haplotype is associated with height. Further investigation in larger populations is needed to clarify the involvement of MCP-1 in MetS.

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Section: Metabolic Syndrome and Parameters From Idf Definitionmentioning

confidence: 49%

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Sedlmeier¹,

Grallert²,

Huth³

et al. 2007

eur j endocrinol

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“…CCR2 is mainly expressed at relatively low levels on monocytes [3-4 ϫ 10 3 molecules per cell (Mine et al, 2006)] but can be drastically increased on natural killer cells (Hanna et al, 2005) and T cells (Amoura et al, 2003) in disease. Here we used transfected HEK293 cells expressing approximately 2 ϫ 10 3 receptors per cell as determined with fluorescent standardization beads (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Different Effects of the Different Natural CC Chemokine Receptor 2b Ligands on β-Arrestin Recruitment, Gα_iSignaling, and Receptor Internalization

Berchiche¹,

Gravel²,

Pelletier³

et al. 2010

Mol Pharmacol

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The chemokine receptor CCR2, which has been implicated in a variety of inflammatory, autoimmune, and cardiovascular conditions, binds several natural chemokine ligands. Here, we assessed the recruitment of ␤-arrestin to CCR2 in response to these ligands using bioluminescence resonance energy transfer technology. Compared with CCL2, which was considered as a full agonist, other CCR2 ligands were partial agonists with reduced efficacy and potency. Agonist potencies were not a function of their affinity for CCR2. Efficacy of arrestin recruitment matched that of agonist-induced CCR2 internalization. Although the potency and efficacy rank orders of the ligands in arrestin recruitment were similar to those observed for G␣ i1 activation, arrestin recruitment was at least in part resistant to G␣ i/o -inactivating pertussis toxin, suggesting partial independence from G␣ i/o . The degree of pertussis toxin resistance of arrestin recruitment was different between the chemokines. Moreover, qualitative differences between the arrestin responses to the different ligands were identified in the stability of the response: although CCL7-induced arrestin recruitment had a halflife of less than 15 min, CCL8 and CCL13 induced stable CCR2-arrestin interactions. Finally, the ligands stabilized different conformations of the CCR2 homodimer. Our results support the validity of models for receptor-ligand interactions in which different ligands stabilize different receptor conformations also for endogenous receptor ligands, with corresponding implications for drug development targeting CCR2.

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“…However, the MCP-1 level increases in endothelial cells when they receive a variety of stresses such as consecutive hyperglycemic conditions in diabetic patients [8][9][10] and TNF-a. 17,[20][21][22] Moreover, it has been shown that CC chemokine receptor (CCR2), the specific receptor of MCP-1, appeared in these cells, and plays essential roles in angiogenesis and proliferation of the vascular wall cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Monocyte Chemoattractant Protein-1 by Krueppel-Like Factor 5 Small Interfering RNA in the Tumor Necrosis Factor- .ALPHA.-Activated Human Umbilical Vein Endothelial Cells

Kumekawa

Fukuda

Shimizu

et al. 2008

Biological & Pharmaceutical Bulletin

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Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus

Cited by 67 publications

References 25 publications

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Different Effects of the Different Natural CC Chemokine Receptor 2b Ligands on β-Arrestin Recruitment, Gα_iSignaling, and Receptor Internalization

Inhibition of Monocyte Chemoattractant Protein-1 by Krueppel-Like Factor 5 Small Interfering RNA in the Tumor Necrosis Factor- .ALPHA.-Activated Human Umbilical Vein Endothelial Cells

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Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus

Cited by 67 publications

References 25 publications

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg

Different Effects of the Different Natural CC Chemokine Receptor 2b Ligands on β-Arrestin Recruitment, GαiSignaling, and Receptor Internalization

Inhibition of Monocyte Chemoattractant Protein-1 by Krueppel-Like Factor 5 Small Interfering RNA in the Tumor Necrosis Factor- .ALPHA.-Activated Human Umbilical Vein Endothelial Cells

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Different Effects of the Different Natural CC Chemokine Receptor 2b Ligands on β-Arrestin Recruitment, Gα_iSignaling, and Receptor Internalization