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)

There is a growing interest in the role of chemokines and their receptors in the determination of mast cell tissue localization and how chemokines regulate mast cell function. At least nine chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CX3CR1, CCR1, CCR3, CCR4 and CCR5) have been described to be expressed by human mast cells of different origins. Seven chemokines (CXCL1, CXCL5, CXCL8, CXCL14, CX3CL1, CCL5 and CCL11) have been shown to act on some of these receptors and to induce mast cell migration. Mast cells have a unique expression pattern of CCR3, CXCR1 and CXCR2. These receptors are mainly expressed intracellularly on cytoplasmic membranes. Upon an allergic activation, CCR3 expression is increased on the cell surface and the cell becomes vulnerable for CCL11 treatment. Chemokines do not induce mast cell degranulation but CXCL14 causes secretion of de novo synthesized CXCL8. Because of the expression of CCR3, CCR5 and CXCR4 on mast cell progenitors, these cells are susceptible to HIV infection and mast cells might therefore be a persistent HIV reservoir in AIDS. In this review, we summarize the knowledge about chemokine receptor expression and function on mast cells.
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PMID:Chemokine receptor expression by mast cells. 1610 68

Psoriasis is an immune-mediated skin disease characterized by lymphocytic infiltration and altered keratinocyte differentiation. Using immunohistochemical techniques we found that the cellular infiltrate in acute psoriatic plaques includes 5-8% CD3(-)CD56(+) natural killer (NK) cells, mostly localized in the mid and papillary dermis. NK lymphocytes isolated from punch biopsy specimens of psoriatic plaques showed a CD56(bright)CD16(-)CD158b(-) phenotype, failed to express the skin homing cutaneous lymphocyte-associated antigen and released abundant IFN-gamma upon stimulation. Supernatants from psoriatic NK cells induced MHC class II and ICAM-1 expression and release of CXCL10 and CCL5 by cultured psoriatic keratinocytes. Skin NK cells expressed high levels of the chemokines receptors CXCR3 and CCR5, intermediate amounts of CXCR1, CCR6 and CCR8, and low levels of CCR1, CCR2, CCR4, CCR7 and CX3CR1. In addition, they promptly migrated in vitro toward CXCL10, CCL5, supernatants of IFN-gamma-activated psoriatic keratinocytes and, to a lower extent, CCL20 and CCL4. In contrast, they failed to migrate toward CXCL8, CCL1, CCL2, CCL3, CCL17, CCL19 and CX3CL1. Taken together, our results implicate NK lymphocytes as newly identified protagonists in the pathogenesis of psoriasis. Their distinctive homing properties should be taken into account in the design of specific therapy aimed at blocking pathogenic cell accumulation in the skin.
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PMID:CD56brightCD16(-) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation. 1632 44

Hyaluronan (HA), in the bone marrow stroma, is the major non-protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor-mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h-MSCs) and a three-dimensional (3-D) HA-based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL-8)/CXCR1-2, CXCL10 (IP-10)/CXCR3, CXCL12 (SDF-1)/CXCR4, and CXCL13 (BCA-1)/CXCR5, and metalloproteinases/inhibitors MMP-1, MMP-3, MMP-13/TIMP-1 were evaluated in h-MSCs grown on plastic or on HA-based scaffold by Real-time PCR, ELISA, and immunocytochemical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA-based scaffold induced the expression of CXCR4, CXCL13, and MMP-3 and downmodulated the expression of CXCL12, CXCR5, MMP-13, and TIMP-1 while HA-based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCL12, CXCL13, and CXCR5. This study demonstrates a direct action of a 3-D HA-based scaffold, widely used for cartilage and bone repair, in modulating both h-MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3-D conformation acts as a signaling molecule for h-MSCs.
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PMID:Hyaluronan-based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54. 1633 75

In this study, we examined the gene expression of interleukin (IL)-8, CXCR3, and CXCR4 in leukemic cells from 100 children with relapsed B-cell progenitors (BCP) acute lymphoblastic leukemia (ALL), using quantitative real-time polymerase chain reaction (RT-PCR). IL-8, CXCR3, and CXCR4 were expressed in almost all bone marrow (BM) samples. The CXCR4 expression significantly correlated with known prognostic factors at relapse: time point and site of relapse. Patients who had a combined BM relapse (n=21) had lower IL-8 and CXCR4 expression than those who had an isolated BM relapse (n=79). The CXCR3 expression was higher in female patients (n=39) than in male patients (n=61). However, this did not reach prognostic relevance in relapsed ALL.
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PMID:Chemokine IL-8 and chemokine receptor CXCR3 and CXCR4 gene expression in childhood acute lymphoblastic leukemia at first relapse. 1667 18

Chronic or recurrent inflammation plays a role in the development of many types of cancer including prostate cancer. CXCL10 (interferon-gamma inducible protein-10, IP-10) is a small secretory protein of 8.7 kDa. Recently, it has been shown that normal prostate epithelial (PZ-HPV-7) cells produce lower amounts of angiogenic CXC chemokines (GRO-alpha, IL-8) and higher amounts of angiostatic chemokines (CXCL10, CXCL11) as compared to prostate cancer cells (CA-HPV-10 and PC-3). Accordingly, we studied the effects of overexpression of CXCL10 in human prostate cancer LNCaP cells. LNCaP cells were transiently transfected with CXCL10 cDNA in pIRES2-EGFP vector. CXCL10, CXCR3, PSA and G3PDH mRNA levels were determined by semi-quantitative conventional and quantitative real-time RT-PCR and fluorescence-activated cell sorting (FACS). The expression of CXCL10 was markedly enhanced in the transfected cells at mRNA and protein levels in the cells. Overexpression of CXCL10 inhibited cell proliferation of the transfected cells by 30%-40% in serum-limited medium (1% FCS in RPMI1640 medium) and decreased PSA production. CXCR3 expression was significantly induced by the overexpression of CXCL10 as determined by RT-PCR and FACS. These results indicated that CXCL10 inhibited LNCaP cell proliferation and decreased PSA production by up-regulation of CXCR3 receptor. CXCL10 may be potentially useful in the treatment of prostate cancer.
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PMID:Overexpression of CXCL10 in human prostate LNCaP cells activates its receptor (CXCR3) expression and inhibits cell proliferation. 1693 57

Infiltration by mononuclear cells is found within the renal tissue in various types of kidney diseases. The migration of leukocytes through vessels and beyond the vascular compartment is dependent in part on small chemoattractant proteins called chemokines. All types of renal cells can produce chemokines in a cell- and stimulus-specific manner. Some chemokines appear to be constitutively expressed, while proinflammatory chemokines are expressed only in responses to specific stimuli. MCP-1 expression in renal tubuli is enhanced in proteinuric states, irrespective of the types of renal disease, and this increased MCP-1 expression probably contributes to renal tubular damage in proteinuric states. Expression of individual chemokines correlate with intrarenal T cells and monocyte/macrophage infiltrates as well as with interstitial kidney damage and renal function. Experimental data and studies on human renal tissue in patients with glomerulonephritis and renal allograft rejection indicate that MCP-1, MIP-lalpha, beta, RANTES, and IL-8 play a main role in the resolution and progression of inflammatory processes in these cases. Renal cells and inflammatory cells also express chemokine receptors, especially CCR-5, CCR-1, CCR-2, and CXCR3. Analysis of the immunoexpression of chemokines and chemokine receptors in renal tissue of patients with glomerulonephritis and renal allograft rejection may be helpful in evaluating the progression of kidney disease, whereas monitoring chemokines in the urine may provide a dynamic picture of the inflammatory state. The pharmacological regulation of chemokine and chemokine receptor expression may be a useful tool in the therapy of kidney diseases.
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PMID:Chemokines and chemokine receptors in glomerulonephritis and renal allograft rejection. 1726 94

The recruitment of bone marrow CD34- mesenchymal stem- and progenitor cells (MSC) and their subsequent differentiation into distinct tissues is the precondition for in situ tissue engineering. The objective of this study was to determine the entire chemokine receptor expression profile of human MSC and to investigate their chemotactic response to the selected chemokines CCL2, CXCL8 and CXCL12. Human MSC were isolated from iliac crest bone marrow aspirates and showed a homogeneous population presenting a typical MSC-related cell surface antigen profile (CD14-, CD34-, CD44+, CD45-, CD166+, SH-2+). The expression profile of all 18 chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that MSC express CC, CXC, C and CX(3)C receptors. Gene expression and immunohistochemical analysis documented that MSC express chemokine receptors CCR2, CCR8, CXCR1, CXCR2 and CXCR3. A dose-dependent chemotactic activity of CXCR4 and CXCR1/CXCR2 ligands CXCL12 and CXCL8 (interleukin-8) was demonstrated using a 96-well chemotaxis assay. In contrast, the CCR2 ligand CCL2 (monocyte chemoattractant protein-1, MCP-1) did not recruited human MSC. In conclusion, we report that the chemokine receptor expression profile of human MSC is much broader than known before. Furthermore, for the first time, we demonstrate that human MSC migrate upon stimulation with CXCL8 but not CCL2. In combination with already known data on MSC recruitment and differentiation these are promising results towards in situ regenerative medicine approaches based on guiding of MSC to sites of degenerated tissues.
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PMID:Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. 1729 3

CXCR3 ligands were secreted by tissue fibroblasts and peripheral blood-derived mononuclear leukocytes in response to interferon-gamma (IFN-gamma) and Toll-like receptor (TLR) ligands. Subsequent purification and identification revealed the presence of truncated CXCL11 variants missing up to 6 amino acids. In combination with CD26/dipeptidyl peptidase IV, the metalloprotease aminopeptidase N (APN), identical to the myeloid cell marker CD13, rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms. Truncated CXCL11 had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. CD13/APN-truncated CXCL11 failed to induce an intracellular calcium increase but was still able to bind and desensitize CXCR3 for intact CXCL11 signaling. CXCL11 efficiently bound to CXCR7, but CXCL11 was not able to induce calcium signaling or ERK1/2 or Akt phosphorylation through CXCR7. CD26-truncated CXCL11 failed to attract lymphocytes but still inhibited microvascular endothelial cell (HMVEC) migration. However, further processing of CXCL11 by CD13 resulted in significant reduction of inhibition of HMVEC migration. Taken together, during inflammation or cancer, CXCL11 processing by CD13 may lead to a reduced number of tumor-infiltrating lymphocytes and in a more angiogenic environment.
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PMID:Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration. 1736 34

Recent evidence indicates that cancer cells express chemokine (CK) receptors and that their signaling is crucial for tumor proliferation, migration, and angiogenesis. The profiles of expression of CXC CK receptors (CXCR1-5) and their main ligands (growth-related oncogene, GRO1-2-3/CXCL1-2-3; interleukin 8, IL-8/CXCL8; monokine-induced gamma-interferon MIG/CXCL9; gamma-interferon-inducible-protein-10, IP-10/CXCL10; stromal cell-derived factor-1, SDF1/CXCL12; B-cell activating CK-1, BCA-1/CXCL13) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) in surgical samples of human meningiomas. All the five receptors displayed high percentages of positive cases: 92% CXCR1, 89% CXCR2, 83% CXCR3, 78% CXCR4, and 94% CXCR5. Conversely, their ligands showed a lower pattern of expression: 40% IL-8, 42% GRO1-3, 42% IP-10, 28% MIG, 53% SDF1, and 3% BCA-1. SDF1/CXCR4 interaction plays a pivotal role in cancer proliferation. Thus, the signaling mechanisms activated by the exclusive binding between SDF1 and CXCR4 was investigated in 12 primary cultures from meningioma tissues. CXCR4 was functionally coupled as demonstrated by the significant increase of DNA synthesis in meningioma cells in response to SDF1, measured by [3H]-thymidine uptake. In three primary cultures, the SDF1-dependent mitogenic activity was associated with a marked phosphorylation of extracellular signal-regulated kinase (ERK1/2) as evaluated by Western blots. PD98059 (a MEK inhibitor) significantly reduced ERK1/2 activation, thus linking the SDF1/CXCR4 pathway to meningioma cell proliferation via ERK1/2 signal transduction. We demonstrate, for the first time in human meningiomas, the simultaneous expression of CXCR1-5 and their CKs and the mitogenic activity of SDF1/CXCR4, suggesting a pivotal role of these receptor-ligand pairs in meningeal tumors.
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PMID:CXC receptor and chemokine expression in human meningioma: SDF1/CXCR4 signaling activates ERK1/2 and stimulates meningioma cell proliferation. 1738 78

CXCL10 was recently shown to exert antimalignancy functions by influencing the tumor microenvironment. Here, we have taken a different approach, investigating the effects of CXCL10 directly on tumor-promoting functions in colorectal carcinoma (CRC) cells. CXCL10 expression was detected in preferred metastatic sites of CRC (liver, lungs, and lymph nodes), and its CXCR3 receptor was expressed by eight CRC cell lines (detected: reverse transcription-PCR and/or flow cytometry). Detailed analysis was done on two cell lines derived from primary CRC tumors (SW480, KM12C) and their metastatic descendents (SW620 and KM12SM). The three known variants of CXCR3 (CXCR3-A, CXCR3-B, and CXCR3-alt) were detected in all four cell lines. CXCR3 expression was also observed on colorectal tumor cells in biopsies of CRC patients (immunohistochemistry). CXCL10 and CXCR3 expression were potently induced in CRC cells by Interferon gamma and all four CRC cell lines responded to CXCL10 by extracellular signal-regulated kinase 1/2 dephosphorylation. The chemokine did not affect tumor cell growth or angiogenesis-related functions in the tumor cells, such as CXCL8 and vascular endothelial growth factor secretion. Importantly, CXCL10 significantly up-regulated invasion-related properties in CRC cells: It promoted matrix metalloproteinase 9 expression and induced CRC cell migration. Of note, CXCL10-induced migration was detected only in the two metastatic cells and not in their primary counterparts. Also, CXCL10 promoted the adhesion of metastatic cells to laminin. These results suggest that CXCL10 can be exploited by CRC cells toward their progression, thus possibly antagonizing the antimalignancy effects of the chemokine on the tumor microenvironment. Therefore, care should be taken when considering CXCL10 as a therapeutic antitumor modality for CRC treatment.
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PMID:CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. 1740 50


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