Macrophage-derived Chemokine (C-C motif) ligand 24 (CCL24) promotes cardiac fibrosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE300219 | GEO | 2025/09/17
REPOSITORIES: GEO
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Project description:Macrophage-derived Chemokine (C-C motif) ligand 24 (CCL24) promotes cardiac fibrosis
| PRJNA1279855 | ENA
Project description:CCL24 is a profibrotic, proinflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease. Mdr2-/- mice demonstrated CCL24 expression in liver macrophages and were used as a relevant experimental PSC model. CCL24 neutralizing monoclonal antibody, CM-101, significantly improved inflammation, fibrosis and cholestasis-related markers in the biliary area. Moreover, using spatial transcriptomics we observed reduced proliferation and senescence of cholangiocytes following CCL24 neutralization. Next, we demonstrated that CCL24 expression was elevated under profibrotic conditions in primary human cholangiocytes and macrophages and it induced proliferation of primary human hepatic stellate cells and cholangiocytes, which was attenuated following CCL24 inhibition. Correspondingly, CCL24 was found to be highly expressed in liver biopsies of PSC patients. CCL24 serum levels correlated with Enhanced Liver Fibrosis score, most notably in patients with high alkaline phosphatase levels. These results suggest that blocking CCL24 may have a therapeutic effect in PSC patients via reduced liver inflammation, fibrosis and cholestasis.
2023-04-30 | GSE228596 | GEO
Project description:The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL. The objective of this study was to investigate the function of CXCL12 in the PDL with rapid turnover.Microarray analysis was performed using a Whole Human Genome 8x60K (Agilent Technologies, Tokyo, Japan) containing approximately 44,000 transcripts. According to the manufacturerM-bM-^@M-^Ys protocol, total RNAs from HPDLFs and HDFs were labeled with Cy3 and hybridized on the microarray. The hybridization data for HPDLFs were compared with data for HDFs.
2013-11-07 | E-GEOD-52162 | biostudies-arrayexpress
Project description:Cardiac resident macrophages (CRM) are essential for cardiac homeostais and physiological/pathological responses. CRM of high-fat diet fed mice or aged mice were sorted by FACS and subjected to SMART-seq.
2024-01-24 | GSE253651 | GEO
Project description:We examined interrelationships between chemokine C-C motif ligand 2 (CCL2) genotype and expression of inflammatory markers in the cerebrospinal fluid (CSF), plasma viral load, CD4 cell count and neurocognitive functioning among HIV-infected adults. We hypothesized that HIV-positive carriers of the 'risk' CCL2 -2578G allele, caused by a single nucleotide polymorphism (SNP) at rs1024611, would have a higher concentration of CCL2 in CSF, and that CSF CCL2 would be associated with both higher concentrations of other proinflammatory markers in CSF and worse neurocognitive functioning.A cross-sectional study of 145 HIV-infected individuals enrolled in the National NeuroAIDS Tissue Consortium cohort for whom genotyping, CSF and neurocognitive data were available.Genomic DNA was extracted from peripheral blood mononuclear cells and/or frozen tissue specimens. CSF levels of CCL2, interleukin (IL)-2, IL-6, tumour necrosis factor-alpha (TNF-?), interferon-gamma (IFN-?), soluble tumor necrosis factor receptor 2, sIL-6R?, sIL-2, sCD14 and B-cell activating factor were quantified. Neurocognitive functioning was measured using a comprehensive battery of neuropsychological tests.Carriers of the CCL2 -2578G allele had a significantly higher concentration of CCL2 in CSF. CSF CCL2 level was positively and significantly associated with other CSF neuroinflammatory markers and worse cognitive functioning. There was a significant association between genotype and plasma viral load, such that carriers of the CCL2 -2578G allele with high viral load expressed greater levels of CCL2 and had higher neurocognitive deficit scores than other genotype/viral load groups.Individuals with the CCL2 -2578G allele had higher levels of CCL2 in CSF, which was associated with increased pro-inflammatory markers in CSF and worse neurocognitive functioning. The results highlight the potential role of intermediate phenotypes in studies of genotype and cognition.
| S-EPMC4573552 | biostudies-literature
Project description:The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.
2013-11-07 | GSE52162 | GEO
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.
| S-EPMC9175512 | biostudies-literature
Project description:BackgroundMonokines induced by interferon-gamma/Chemokine (C-X-C motif) ligand 9 (MIG/CXCL9), thymus and activation-regulated chemokine/Chemokine (C-C motif) ligand 17 (TARC/CCL17) are chemotactic factors that specifically collect and activate leukocytes, which are considered as chemoattractants of T helper cells. In the present study, we have investigated the effects of T helper type-1 (Th1) cells and T helper type-2 (Th2) cells in Kawasaki disease (KD) by determining plasma levels of MIG/CXCL9 and TARC/CCL17 and exploring the relationship between MIG/CXCL9, TARC/CCL17 levels and coronary artery lesions (CAL).MethodsForty-three children patients with KD and 19 healthy controls were included in this study. General characteristics were obtained from all subjects. Plasma concentrations of chemotactic factors of MIG/CXCL9 and TARC/CCL17 were measured by enzyme-linked immunosorbent assay (ELISA) for all subjects.ResultsPlasma levels of MIG/CXCL9, TARC/CCL17, and the ratios of MIG/TARC were significantly elevated in pediatric patients with KD compared to those in the control group. There were also significantly higher levels of MIG/CXCL9, TARC/CCL17, MIG/TARC ratios and prominently lower hemoglobin (Hb) levels in KD with CAL compared to KD without coronary artery lesions (NCAL). Hb was significantly decreased and plasma MIG/CXCL9 levels had a significantly negative correlation with CRP in KD with CAL patients (KD-CAL), whereas a positive correlation of plasma MIG/CXCL 9 with WBC was observed in KD without CAL patients (KD-NCAL).ConclusionTh1 and Th2 cells may be involved in an imbalanced activation in pediatric KD patients during an acute period of the disease. Furthermore, immune lesions of vessels in KD patients may be mediated by the imbalanced activation of Th1 and Th2 cells.
| S-EPMC4560122 | biostudies-literature
Project description:Understanding transcriptional regulatory networks requires the identification and characterization of cis-regulatory modules (CRMs), DNA sequences which can direct expression of associated genes to a specific cell type and/or developmental stage. Reporter assays for the capacity of a candidate CRM to activate a heterologous promoter have been productive but suffer limited throughput or fail to convey information on cell type specificity. We have developed an assay in which reporter constructs containing a pool of candidate CRMs are introduced in parallel to Drosophila embryos along with a common cell-type-specific second marker; candidate CRMs isolated by PCR from FACS-purified double-positive cells can by quantitated by high-throughput sequencing, and their relative abundance compared to those in the input cell population to detect activity in the cell type (or types) of interest.
2013-07-13 | GSE41503 | GEO
Project description: Not available
| S-EPMC10671276 | biostudies-literature