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

The CC chemokine eotaxin/CCL11 is known to bind to the receptor CCR3 on eosinophils and Th2-type lymphocytes. In this study, we demonstrate that CCR3 is expressed on a subpopulation of primary human dermal microvascular endothelial cells and is up-regulated by TNF-alpha. We found that incubation of human dermal microvascular endothelial cells with recombinant eotaxin/CCL11 suppresses TNF-alpha-induced production of the neutrophil-specific chemokine IL-8/CXCL8. The eotaxin/CCL11-suppressive effect on endothelial cells was not seen on IL-1beta-induced IL-8/CXCL8 release. Eotaxin/CCL11 showed no effect on TNF-alpha-induced up-regulation of growth-related oncogene-alpha or IFN-gamma-inducible protein-10, two other CXC chemokines tested, and did not affect production of the CC chemokines monocyte chemoattractant protein-1/CCL2 and RANTES/CCL5, or the adhesion molecules ICAM-1 and E-selectin. These results suggest that eotaxin/CXCL11 is not effecting a general suppression of TNF-alphaR levels or signal transduction. Suppression of IL-8/CXCL8 was abrogated in the presence of anti-CCR3 mAb, pertussis toxin, and wortmannin, indicating it was mediated by the CCR3 receptor, G(i) proteins, and phosphatidylinositol 3-kinase signaling. Eotaxin/CCL11 decreased steady state levels of IL-8/CXCL8 mRNA in TNF-alpha-stimulated cells, an effect mediated in part by an acceleration of IL-8 mRNA decay. Eotaxin/CCL11 may down-regulate production of the neutrophil chemoattractant IL-8/CXCL8 by endothelial cells in vivo, acting as a negative regulator of neutrophil recruitment. This may play an important biological role in the prevention of overzealous inflammatory responses, aiding in the resolution of acute inflammation or transition from neutrophilic to mononuclear/eosinophilic inflammation.
 ...
PMID:Eotaxin/CCL11 suppresses IL-8/CXCL8 secretion from human dermal microvascular endothelial cells. 1188 59

The structure of IP-10 was solved by NMR spectroscopy and represents the first structure from the class of agonists toward the receptor CXCR3. CXCR3 binding chemokines are unique in their ability to bind receptors from both the CC and CXC classes of chemokine receptors. An unusual structural feature of IP-10 was identified that may provide the basis for the ability of IP-10 to bind both CXCR3 and CCR3. The surface of IP-10 that interacts with the N-terminus of CXCR3 was defined by monitoring changes in the NMR spectrum of IP-10 upon addition of a CXCR3 N-terminal peptide. These studies indicated that the interaction involves a hydrophobic cleft, formed by the N-loop and 40s-loop region of IP-10, similar to the interaction surface observed for other chemokines such as IL-8. An additional region of interaction was observed that consists of a hydrophobic cleft formed by the N-terminus of IP-10 and 30s-loop of IP-10.
 ...
PMID:The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. 1217 28

The brain is a target organ for recreational drugs and HIV-1. Epidemiological data demonstrate that opioid abuse is a risk factor for HIV-1 infection and progression to AIDS. Chemokines and their receptors have been implicated in the neuropathogenesis of HIV-1 infections. However, little is known about the effects of opioids on the expression of chemokines and their receptors (the latter also are HIV-1 coreceptors) by cells of the CNS. Herein we describe the effects of morphine on gene expression of the alpha- and beta-chemokines and their receptors by the astrocytoma cell line U87 and by primary normal human astrocyte (NHA) cultures. U87 cells treated with morphine showed significant down-regulation of IL-8 gene expression, whereas expression of the IL-8 receptor CXCR2 was reciprocally up-regulated as detected by RT-PCR. Treatment of NHAs with morphine suppressed IL-8 and macrophage-inflammatory protein-1beta gene expression, whereas expression of their receptor genes, CCR3 and CCR5, was simultaneously enhanced. These morphine-induced effects on U87 and NHA cells were reversed by the opioid mu receptor antagonist beta-funaltrexamine. Morphine also enhanced the constitutive expression of the opioid mu receptor on astroglial cells. Our results support the hypothesis that opioids play a significant role in the susceptibility of the CNS to HIV-1 infection and subsequent encephalopathy by inhibiting local production of HIV-1-protective chemokines (IL-8 and macrophage-inflammatory protein-1beta) and enhancing expression of HIV-1 entry coreceptor genes (CCR3, CCR5, and CXCR2) within the CNS. These effects of opioids appear to be mediated through the opioid mu receptor that we demonstrated on astroglial cells.
 ...
PMID:Morphine regulates gene expression of alpha- and beta-chemokines and their receptors on astroglial cells via the opioid mu receptor. 1224 49

Human Vgamma9/Vdelta2(+) T lymphocytes participate in the immune response against intracellular pathogens through the secretion of type-1 cytokines and chemokines and by killing of infected cells. Little is known of the effects by type-2 differentiation of gamma delta cells on these functions. Here, we report that bona fide naive cord blood-derived gamma delta lymphocytes expanded in vitro with the mycobacterial antigen isopentenyl pyrophosphate (IPP) can be differentiated as either type-1 or type-2 cells, in the presence of an appropriate cytokine milieu. Instead, peripheral gamma delta cells from PPD-negative healthy adults displayed a type-1 cytokine profile, i.e. IPP-stimulated secretion of IFN-gamma, but not of IL-4 and IL-10. Moreover, they released the macrophage inflammatory protein (MIP)-1beta, but not IL-8 nor the Th2 chemoattractants I-309 and TARC (thymus and activation-regulated chemokine). This cytokine profile was not significantly affected by in vitro culture in Th2 polarizing conditions. Only in one case out of seven were peripheral gamma delta cells fully differentiated to type-2 lymphocytes, characterized by sustained IL-4 and IL-10 production, along with secretion of substantial amounts of IL-8, I-309 and TARC. Type-2 gamma delta T lymphocytes preferentially expressed the co-stimulatory molecule CD30; conversely, no skewing in chemokine receptor expression was observed. Both polarized populations displayed high levels of CXCR3 in the absence of CCR3, CCR4 and CCR5. Finally, type-1, but not type-2, gamma delta T lymphocytes killed IPP-pulsed U937 cells and displayed elevated perforin content. Overall, our data suggest that type-2 differentiation of gamma delta T lymphocytes profoundly affects both their effector functions and their potential to recruit the appropriate leukocyte subsets to the sites of inflammation.
 ...
PMID:Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 gamma delta T lymphocytes. 1235 47

Chemokines are key mediators of the selective migration of leukocytes that occurs in neurodegenerative diseases and related inflammatory processes. Astrocytes, the most abundant cell type in the CNS, have an active role in brain inflammation. To ascertain the role of astrocytes during neuropathological processes, we have investigated in two models of primary cells (human fetal and simian adult astrocytes) the repertoire of chemokines and their receptors expressed in response to inflammatory stimuli. We demonstrated that, in the absence of any stimulation, human fetal and simian adult astrocytes express mRNA for receptors APJ, BOB/GPR15, Bonzo/CXCR6, CCR2, CCR3, CCR5, CCR8, ChemR23, CXCR3/GPR9, CXCR4, GPR1, and V28/CX3CR1. Moreover, TNFalpha and IL-1beta significantly increase BOB/GPR15, CCR2, and V28/CX3CR1 mRNA levels in both models. Furthermore, TNFalpha and IFNgamma act synergistically to induce expression of the major coreceptors for HIV infection, CXCR4 and CCR5, at both the mRNA and protein levels in human and simian astrocytes, whereas CCR3 expression was not affected by cytokine treatment. Finally, TNFalpha/IFNgamma was the most significant cytokine combination in leading to a pronounced upregulation in a comparable, time-dependent manner of the production of chemokines IP-10/CXCL10, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IL-8/CXCL8. In summary, these data suggest that astrocytes serve as an important source of chemokines under the dependence of a complex cytokine regulation, and TNFalpha and IFNgamma are important modulators of chemokines and chemokine receptor expression in human as well as simian astrocytes. Finally, with the conditions we used, there was no difference between species or age of tissue.
 ...
PMID:Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation. 1255 3

Within the brain, quinolinic acid (QUIN) is an important neurotoxin, especially in AIDS dementia complex (ADC). Its production by monocytic lineage cells is increased in the context of inflammation. However, it is not known whether QUIN promotes inflammation. Astrocytes are important in immunoregulation within the brain and so we chose to examine the effects of QUIN on the astrocyte. Using purified primary human fetal astrocyte cultures, we determined chemokine production using ELISA assays and RT-PCR and chemokine receptor expression using immunocytochemistry and RT-PCR with QUIN in comparison to TNFalpha, IL-1beta, and IFNgamma. We found that QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2) and lesser amounts of RANTES (CCL5) and IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9), and fractalkine (CX(3)CL1) mRNA expression. Moreover, QUIN leads to upregulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3 in human fetal astrocytes. Most of these effects were comparable to those induced by TNFalpha, IL-1beta, and IFNgamma. The present work represents the first evidence that QUIN induces chemokine and chemokine receptor expression in astrocytes and is at least as potent as classical mediators such as inflammatory cytokines. These results suggest that QUIN may be critical in the amplification of brain inflammation, particularly in ADC.
 ...
PMID:Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes. 1255 4

The expression and the functional activities of different chemokine receptors (CC motif: CCR1, CCR2, CCR3, CCR5, CCR6; CXC motif: CXCR1, CXCR2, CXCR3, CXCR4, CXCR5) were investigated in 12 patients with lymphoproliferative disease of granular lymphocytes (LDGL). Six patients were characterized by the proliferation of CD3+ve GL and six patients by the expansion of CD3-ve GL. The interleukin 8 (IL-8/CXCL8) receptor CXCR1 was expressed in 12/12 patients, the CXCR4 in 6/12 patients (four CD3+ve and two CD3-ve) and the CXCR3 in 3/12 patients (one CD3+ve and two CD3-ve). CXCR1 was expressed only by proliferating GL. Other CC and CXC receptors were not expressed on proliferating GL (< 2%). In functional assays, purified GL from the patients displayed significant migration in response to specific chemokines, indicating that CXCR1, CXCR3 and CXCR4 were functionally active in these patients. In addition, a significant reduction of IL-8/CXCL8-mediated cell migration was reported in the presence of anti-CXCR1 monoclonal antibody. Our results indicate that expanding cells from patients with LDGL express specific CXCR. These data may help to define functional properties of proliferating GL in patients with LDGL and contribute toward the understanding of the complex clinical features of this disease. In particular, as CXCR1 was expressed in all of the patients studied, we speculate that abnormal expression of this receptor on proliferating GL might play a role in the pathogenesis of neutropenia, which represents a common feature in LDGL patients.
 ...
PMID:Upregulation of CXCR1 by proliferating cells in patients with lymphoproliferative disease of granular lymphocytes. 1261 7

The CXC chemokine IFN-gamma-inducible protein-10 (IP-10/CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer cells. Peripheral blood mononuclear cells (PBMC) produce low but significant amounts of IP-10/CXCL10 protein upon stimulation with double-stranded (ds) RNA, the Toll-like receptor 3 (TLR3) ligand. IFN-gamma is a superior IP-10/CXCL10inducer. The bacterial TLR4 and TLR2 ligands, LPS and peptidoglycan (PGN), inhibit IFN-gamma- or dsRNA-dependent IP-10/CXCL10 production in PBMC, whereas IL-8/CXCL8 production was enhanced. In fibroblasts a different picture emerges with IFN-gamma inducing moderate and dsRNA provoking strong IP-10/CXCL10 production. Furthermore, treatment of fibroblasts with IFN-gamma in combination with bacterial LPS or PGN results in a synergistic production of IP-10/CXCL10 and IL-8/CXCL8. The synergistic induction of IP-10/CXCL10 in fibroblasts is reflected by significantly enhanced IP-10/CXCL10 concentrations in synovial fluids of septic compared to osteoarthritis patients to reach on average higher levels than those of IL-8/CXCL8. These high amounts of IP-10/CXCL10 produced by connective tissue fibroblasts not only attract CXCR3 expressing activated Th1 cells and natural killer cells to sites of infection but may also antagonize the CCR3 dependent attraction of Th2 lymphocytes and exert CXCR3-independent, defensin-like antibacterial activity.
 ...
PMID:Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10 expression in fibroblasts and mononuclear leukocytes in synergy with IFN-gamma and provide a mechanism for enhanced synovial chemokine levels in septic arthritis. 1457 83

The selective accumulation of different leucocyte populations during inflammation is regulated by adhesion molecules and chemokines expressed by vascular endothelium. This study examined how chemokine production and the expression of adhesion molecules and chemokine receptors vary between endothelia from different vascular beds. Human saphenous vein endothelium was compared with lung and dermal microvascular endothelia and with umbilical vein endothelium and a bone-marrow endothelial cell line. All endothelia produced CCL2 and CXCL8 constitutively, whereas CXCL10 and CCL5 were only secreted after tumour necrosis factor (TNF)-alpha or interferon (IFN)-gamma stimulation. In combination with TNF-alpha, IFN-gamma suppressed CXCL8 but enhanced CCL5 and CXCL10, whereas transforming growth factor (TGF)-beta reduced secretion of all chemokines. Basal chemokine secretion was higher from umbilical vein than other endothelial cells. Chemokine receptors, CXCR1, CXCR3 and CCR3, were present on all endothelia but highest on saphenous vein. CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 were also detected at variable levels on different endothelia. The variation between endothelia in chemokine secretion was much greater than the variations in adhesion molecules, both on resting cells and following cytokine stimulation. These results indicate that it is the tissue-specific variations in endothelial chemokine secretion rather than variations in adhesion molecules that can explain the different patterns of inflammation and leucocyte traffic seen in non-lymphoid tissues.
 ...
PMID:Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration. 1463 48

In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/ or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22-57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-gamma showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.
 ...
PMID:Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test. 1470 3


<< Previous 1 2 3 4 5 Next >>