Dataset Information

Chemokine (C-C motif) ligand 2 (CCL2) in sera of patients with type 1 diabetes and diabetic complications.

ABSTRACT: Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), has been implicated in the pathogenesis of many diseases characterized by monocytic infiltration. However, limited data have been reported on MCP-1 in type 1 diabetes (T1D) and the findings are inconclusive and inconsistent.In this study, MCP-1 was measured in the sera from 2,472 T1D patients and 2,654 healthy controls using a Luminex assay. The rs1024611 SNP in the promoter region of MCP-1 was genotyped for a subset of subjects (1764 T1D patients and 1323 controls) using the TaqMan-assay.Subject age, sex or genotypes of MCP-1 rs1024611SNP did not have a major impact on serum MCP-1 levels in either healthy controls or patients. While hemoglobin A1c levels did not have a major influence on serum MCP-1 levels, the mean serum MCP-1 levels are significantly higher in patients with multiple complications (mean?=?242 ng/ml) compared to patients without any complications (mean?=?201 ng/ml) (p?=?3.5×10(-6)). Furthermore, mean serum MCP-1 is higher in controls (mean?=?261 ng/ml) than T1D patients (mean?=?208 ng/ml) (p<10(-23)). More importantly, the frequency of subjects with extremely high levels (>99(th) percentile of patients or 955 ng/ml) of serum MCP-1 is significantly lower in the T1D group compared to the control group (odds ratio?=?0.11, p<10(-33)).MCP-1 may have a dual role in T1D and its complications. While very high levels of serum MCP-1 may be protective against the development of T1D, complications are associated with higher serum MCP-1 levels within the T1D group.

SUBMITTER: Guan R

PROVIDER: S-EPMC3075244 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Chemokine (C-C motif) ligand 2 (CCL2) in sera of patients with type 1 diabetes and diabetic complications.

Guan Ruili R Purohit Sharad S Wang Hongjie H Bode Bruce B Reed John Chip JC Steed R Dennis RD Anderson Stephen W SW Steed Leigh L Hopkins Diane D Xia Chun C She Jin-Xiong JX

PloS one 20110412 4

<h4>Background</h4>Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), has been implicated in the pathogenesis of many diseases characterized by monocytic infiltration. However, limited data have been reported on MCP-1 in type 1 diabetes (T1D) and the findings are inconclusive and inconsistent.<h4>Methods</h4>In this study, MCP-1 was measured in the sera from 2,472 T1D patients and 2,654 healthy controls using a Luminex assay. The rs1024611 SNP in ...[more]

PMID: 21532752

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Project description:Introduction To a large extent, a person's susceptibility to developing periodontitis is determined by their genetic makeup. Research has shown that chemokines generated during an immune response can harm the periodontal ligaments, gingiva, and alveolar bone. Various chemokine genes located on different chromosomes contribute to periodontitis, and one such gene is C-C motif chemokine ligand 2 (CCL2), associated with the rs1024611 polymorphism, which is part of a cytokine gene cluster on the q-arm of chromosome 17. Objective Our specific objective was to investigate whether CCL2 polymorphisms could influence the relative risk of developing periodontitis. Building on these findings, we aimed to compare the frequency of a specific single nucleotide polymorphism (SNP) in the CCL2 gene between individuals with and without periodontitis. Materials and methods Fifty participants were enrolled in the study after obtaining informed consent and ethical clearance. Clinical assessments, including probing pocket depth, clinical attachment loss, and bleeding on probing, were utilized to classify individuals into two groups: a control group (Group A, n=25) and a periodontitis group (Group B, n=25). DNA extraction from collected samples involved drawing 2 ml of venous blood from the antecubital fossa and transferring it into a sterile tube with a pinch of ethylene diamine tetraacetic acid (EDTA) to prevent clotting. DNA extraction was performed and polymorphisms of CCL2 were assessed through polymerase chain reaction (PCR) and restriction enzyme digestion. Results The periodontitis group consisted of 25 patients, with an average age of 39.0±0.22 years, who met the American Academy of Periodontology's 2018 criteria for at least stage II periodontitis. The control group comprised 25 individuals with an average age of 41.3±0.49 years. Regarding the CCL2 gene polymorphism (rs1024611), there was no substantial variation in genotype frequencies between the patients and controls (p = 0.695). An agarose gel electrophoretogram, along with a standard DNA ladder, demonstrated partial amplification of the CCL2 gene spanning the polymorphism site (rs1024611). Genotypes observed were as follows: homozygous AA - 333 bp; heterozygous AG - 333 + 250 + 73 bp; homozygous GG - 250 + 73 bp. Conclusion In conclusion, there is no significant association between the CCL2 gene polymorphism rs1024611 and susceptibility to periodontitis.

Project description:Background and aimsHepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology-induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis.Approach and resultsHere, we quantified the amount of γδ T cells using a γδ T-cell-specific gene signature in 247 Chinese HCC patients. We also validated the γδ T-cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data, but not in adjacent nontumor transcriptomic data, suggesting a selective enrichment of γδ T cells in the tumor microenvironment. Moreover, the γδ T-cell signature was positively correlated with the expression of natural killer cell receptor genes, such as NKG2D and cytolytic T-cell genes granzymes and perforin, suggesting a stronger T-cell-mediated cytotoxic activity. Furthermore, we found that the γδ T-cell-specific gene expression is positively correlated with the expression of chemokine (C-C motif) ligand 4 (CCL4)/chemokine (C-C motif) ligand 5 (CCL5) and C-C chemokine receptor type 1 (CCR1)/C-C chemokine receptor type 5 (CCR5), the receptors for γδ T cells. We validated these results using immunohistochemical analysis of formalin-fixed, paraffin-embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5-mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1-6 HCC model.ConclusionsWe propose that CCL4/CCL5 may interact with their receptor, CCR1/CCR5, which may facilitate the recruitment of γδ T cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T cells in tumors may enhance antitumor immunity and improve patients' prognosis.

Dataset Information

Chemokine (C-C motif) ligand 2 (CCL2) in sera of patients with type 1 diabetes and diabetic complications.

Publications

Chemokine (C-C motif) ligand 2 (CCL2) in sera of patients with type 1 diabetes and diabetic complications.

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