Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of cytokines and chemokines exert potent myelosuppressive effects that play a role in the maintenance of hematopoiesis, which, if unchecked, may result in pathological impairment of blood cell production. Processes that modulate these myelosuppressive effects are not well defined. Here we demonstrate that stromal cell-derived factor-1 (SDF-1/CXCL12), known for its ability to attract and to promote survival of hematopoietic progenitor cells (HPCs) and stem cells, blocks the effects of a broad range of myelosuppressive chemokines on proliferation of HPCs in vitro. The regulatory effects of SDF/CXCL12 on colony formation by mouse bone marrow granulocyte-macrophage (CFUGM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells were assessed. These cells were stimulated to proliferate by combinations of growth factors, such that responses of immature HPCs could be assessed. SDF-1/CXCL12 potently blocked myelosuppressive responses induced by CCL2/MCP-1, CCL3/MIP-1alpha, CCL19/CKbeta-11, CCL25/TECK, CXCL4/PF4, CXCL8/IL-8, CXCL10/IP-10, and XCL1/Lymphotactin. However, SDF/CDL12 did not influence myelosuppression induced by tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta or the iron-binding proteins H-ferritin or lactoferrin (LF). LF, previously shown to suppress release of growth factors, is shown here to also suppress proliferation of immature subsets of HPCs. HPCs from marrows of mice expressing an SDF-1/CXCL12 transgene were insensitive to inhibition by SDF/CXCL12-sensitive myelosuppressive chemokines, but not to SDF/CCL12-insensitive cytokines (TNF-alpha, IFN-gamma, TGF-beta, H-Ferritin, or LF). Thus, SDF-1/CXCL12 differentially and selectively regulates suppression of HPC proliferation by chemokines. These effects may counter myelosuppressive effects of certain chemokines in vivo, where proliferation of HPCs must be sustained.
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PMID:Stromal cell-derived factor-1/CXCL12 selectively counteracts inhibitory effects of myelosuppressive chemokines on hematopoietic progenitor cell proliferation in vitro. 1591 Feb 46

For bone repair, transplantation of periosteal progenitor cells (PCs), which had been amplified within supportive scaffolds, is applied clinically. More innovative bone tissue engineering approaches focus on the in situ recruitment of stem and progenitor cells to defective sites and their subsequent use for guided tissue repair. Chemokines are known to induce the directed migration of bone marrow CD34(-) mesenchymal stem cells (MSCs). The aim of our study was to determine the chemokine receptor expression profile of human CD34(-) PCs and to demonstrate that these cells migrate upon stimulation with selected chemokines. PCs were isolated from periosteum of the mastoid bone and displayed a homogenous cell population presenting an MSC-related cell-surface antigen profile (ALCAM(+), SH2(+), SH3(+), CD14(-), CD34(-), CD44(+), CD45(-), CD90(+)). The expression profile of chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that PCs express receptors of all four chemokine subfamilies CC, CXC, CX(3)C, and C. Migration of PCs and a dose-dependent migratory effect of the chemokines CCL2 (MCP1), CCL25 (TECK), CXCL8 (IL8), CXCL12 (SDF1alpha), and CXCL13 (BCA1), but not CCL22 (MDC) were demonstrated using a 96-multiwell chemotaxis assay. In conclusion, for the first time, here we report that human PCs express chemokine receptors, present their profile, and demonstrate a dose-dependent migratory effect of distinct chemokines on these cells. These results are promising towards in situ bone repair therapies based on guiding PCs to bone defects, and encourage further in vivo studies.
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PMID:Human periosteum-derived progenitor cells express distinct chemokine receptors and migrate upon stimulation with CCL2, CCL25, CXCL8, CXCL12, and CXCL13. 1850 72

The relationship has become clear between the expression of chemokine/chemokine receptors on cancer cells and the invasion, metastasis and peritoneal dissemination. Many cancer cells express chemokine receptors which are not expressed on the surface of normal tissues. Recently, it has been reported that overexpression of CXCR4/CXCL12 is related with metastasis to lung, liver, lymph nodes and bone marrow, while the overexpression of CCR7/CCL21 is mainly related with lymph node metastasis. We performed a comparative analysis of differential gene expressions related to chemokines/chemokine receptors, and cytokines in established gastric cancer cell lines by cDNA microarray. Upregulated chemokine genes were CCL21, CCL5, CXCL14, CCL2, CXCL1, CXCL8, CXCL7 and CXCL12, which the downregulated chemokines genes were MIP-1alpha and TECK. The upregulated gene of chemokine receptors was CCR-6. In the cancer microenvironment, cancer cells readily formed edematous and inflammatory conditions, easily metastasizing to other organs with the suppression of dendritic cells. The chemokines/chemokine receptors will hopefully become the new targets for cancer therapies for the regulation of metastasis.
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PMID:[Chemokine and chemokine receptor related to cancer metastasis]. 2108 2