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)

The present report compares a variety of T cell purification protocols and chemotaxis procedures in assessing chemokine-induced T cell migration using a microchemotaxis assay. Rapidly purified T cells are capable of directly responding to the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES in the absence of alpha CD3 stimulation as previously described (Taub, D.D. and Oppenheim, J.J. (1993) Cytokine 5, 175). However, T cell purification schemes involving prolonged 37 degrees C incubations generally produce non-motile T lymphocytes that require stimulation with alpha CD3 antibody for 6-12 h in culture to recover chemotactic mobility. This loss of chemotactic potential appears to be due to prolonged 37 degrees C incubations as rapidly purified T cells lose migratory activity upon incubation at 37 degrees C. Radiolabeled binding analysis revealed that beta chemokine binding sites are downregulated as short as 2 h after incubation at 37 degrees C. T cells require the presence of extracellular matrix molecules to facilitate T cell migration. While many of these proteins permit chemotactic activity, human plasma and foreskin fibronectin were found to be the most effective matrix molecule for T cell migration. Kinetic analysis of T cell activation revealed that 6-12 h of anti-CD3 stimulation was optimal to restore the ability of purified T cells to migrate in response to the chemokines MIP-1 alpha, MIP-1 beta, RANTES, and IL-8. However, rapidly dividing T cells (> or = 48 h post alpha CD3 mAb stimulation) fail to migrate in response to any chemotactic stimulus. Together, these results suggest that the measurement of T cell migration, using microchemotaxis chambers, is a multifactorial process with strict environmental and activation requirements.
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PMID:Chemotaxis of T lymphocytes on extracellular matrix proteins. Analysis of the in vitro method to quantitate chemotaxis of human T cells. 754 17

The chemokine beta family is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, macrophage inflammatory protein 1 alpha (MIP-1 alpha), also regulates the growth of hematopoietic stem cells. We now show that MIP-1 alpha and the related beta chemokine, RANTES, induce transient alterations in intracellular Ca2+ concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now cloned both the cDNA and the gene for this receptor, functionally expressed the receptor in Xenopus oocytes, and mapped the gene to human chromosome 3p21. Transcripts for the receptor were found in mature and immature myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has approximately 33% amino acid identity with receptors for the alpha chemokine, interleukin 8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus.
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PMID:Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor. 768 36

T lymphocytes, macrophages, and oxidized low-density lipoprotein (Ox-LDL) are collocalized in early atherosclerotic lesions. Using a low-endotoxin in vitro system, we observed that Ox-LDL but not native LDL induced the production, by both freshly adherent human peripheral blood monocytes and human monocytic THP-1 cells, of the alpha chemokine interleukin (IL)-8, a potent chemoattractant for T lymphocytes. Marked IL-8 induction by Ox-LDL did not require IL-1 beta generation in THP-1 cells. Ox-LDL-induced chemokine production was selective, as Ox-LDL did not stimulate the production by THP-1 cells of the T-lymphocyte chemotactic beta chemokine macrophage inflammatory protein (MIP)-1 alpha. IL-8 induction increased in proportion to the extent of oxidation of LDL as measured by the content of lipid oxidation end products. To identify potentially active components of Ox-LDL, we tested malondialdehyde, an arachidonate-derived lipid oxidation product, and 9-hydroxyoctadecadienoic acid, an oxidation product of linoleate, the major polyunsaturated fatty acid in LDL, and observed that they induced IL-8 generation in the absence of Ox-LDL. Furthermore, when most free lipid oxidation products were removed from Ox-LDL by dialysis, some IL-8-inducing activity was released into the dialysate. However, the major IL-8-inducing activity was not dialyzable. To address the nature of the LDL particle modification required to induce IL-8, acetylated or malondialdehyde-treated native LDL particles were monitored for activity. Neither procedure rendered LDL capable of inducing IL-8. However, phospholipase A2-treated LDL induced THP-1 cell expression of IL-8.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidized LDL induces monocytic cell expression of interleukin-8, a chemokine with T-lymphocyte chemotactic activity. 827 77

Viruses are known to acquire and modify the genes of their hosts to attain a survival advantage in the host environment. Herpesvirus saimiri (HVS) is a T-lymphotropic virus that causes fatal lymphoproliferative diseases in several non-human primates. The gene ECRF3 of HVS was most likely acquired from a primate host. ECRF3 encodes a putative seven-transmembrane-domain receptor that is remotely related (approximately 30% amino acid identity) to the known mammalian alpha and beta chemokine receptors, namely interleukin-8 receptor (IL8R) types A and B and the MIP-1 alpha/RANTES receptor, respectively. Chemokines regulate the trafficking, activation, and, in some cases, proliferation of myeloid and lymphoid cell types. We now show that ECRF3 encodes a functional receptor for the alpha chemokines IL-8, GRO/melanoma growth stimulatory activity (MGSA), and NAP-2 but not for beta chemokines, a specificity identical to that of IL8RB. Paradoxically, IL8RA shares 77% amino acid identity with IL8RB but is not a receptor for GRO/MGSA or NAP-2. This is the first functional characterization of a viral seven-transmembrane-domain receptor. It suggests a novel role for alpha chemokines in the pathogenesis of HVS infection by transmembrane signaling via the product of ECRF3.
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PMID:Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. 840 86

Several chemoattractant receptors can support agonist-induced, integrin-dependent arrest of rolling neutrophils in inflamed venules in vivo, as well as subsequent crawling into tissues. It has been hypothesized that receptors of the Galpha(i)-linked chemoattractant subfamilies, especially receptors for chemokines, may mediate parallel activation-dependent arrest of homing lymphocyte subsets. However, although several chemokines can attract subsets of B or T cells, robust chemoattractant triggering of resting lymphocyte adhesion to vascular ligands has not been observed. To study the biology of individual leukocyte chemoattractant receptors in a defined lymphoid environment, mouse L1/2 pre-B cells and/or human Jurkat T cells were transfected with alpha (IL-8 receptor A) or beta (MIP-1alpha/CC-CKR-1) chemokine receptors, or with the classical chemoattractant C5a (C5aR) or formyl peptide receptors (fPR). All receptors supported robust agonist-dependent alpha4beta1 integrin-mediated adhesion of lymphocytes to VCAM-1. L1/2 cells cotransfected with fPR and beta7 integrin were also induced to bind MAdCAM-1, suggesting common mechanisms coupling chemoattractant receptors to activation of distinct integrins. Adhesion was rapid but transient, with spontaneous reversion to unstimulated levels within 5 min after peak binding. When observed under flow conditions, alpha4beta1-mediated arrest occurred within seconds after initiation of contact and rolling of IL-8RA transfectants on VCAM-1/IL-8 co-coated surface; and arrest reversed spontaneously after a mean of 5 min with a return to rolling behavior. Each of the receptors also conferred agonist-specific chemotaxis; however, whereas strong adhesion required simultaneous occupancy of many receptors with maximal responses above the Kd, chemotaxis in each case was suppressed at high agonist concentrations. The findings indicate that alpha and beta chemokine as well as classical chemoattractant receptors can trigger robust adhesion as well as directed migration of lymphoid cells, but that the requirements for and kinetics of adhesion triggering and chemotaxis are distinct, thus permitting their independent regulation. They suggest that the discordance between proadhesive and chemoattractant responses of circulating lymphocytes to many chemokines may reflect quantitative aspects of receptor expression and/or coupling rather than qualitative differences in receptor signaling.
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PMID:Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells. 869 20

MCP-3 is a beta chemokine consisting of 76 amino acid residues. It has been described to be involved in the activation of all leukocytic cells, activation mediated by the presence of multiple binding sites on the target cells. Its three-dimensional structure has been studied by making use of two-dimensional 1H NMR spectroscopy. MCP-3 exhibits the same monomeric structure as the other chemokines, i.e., a three-stranded antiparallel beta sheet covered on one face by an alpha helix. Although it belongs to the same subfamily as RANTES (Chung et al., 1995; Faitbrother et al., 1994) and hMIP-1beta (Lodi et al., 1994), the MCP-3 dimer is folded like IL-8 with the so-called alphabeta sandwich structural motif. Structural and sequence analysis gives clear indications suggesting that the other MCP chemokines may have the same quaternary structure, contrary to the other beta chemokines.
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PMID:Determination of the three-dimensional structure of CC chemokine monocyte chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy. 910 48

The homing of lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines. Secondary lymphoid-tissue chemokine (SLC), a high endothelial venule (HEV)-associated chemokine, has emerged as a candidate for participating in this process. We now show that immobilized SLC strongly induces beta2 integrin-mediated binding of T lymphocytes of naive phenotype and B lymphocytes to ICAM-1 under static conditions. This effect is not mediated by beta2 integrin affinity modulation, because SLC does not elicit a beta2 integrin activation epitope (mAb24) on naive T lymphocytes. In a parallel plate flow chamber, lymphocytes rolling via L-selectin are rapidly arrested through beta2 integrins in a pertussis toxin-sensitive manner on a substrate consisting of L-selectin ligands (peripheral lymph node addressins) together with ICAM-1 and SLC. Naive T lymphocytes are arrested on the HEV substrate with sixfold higher efficiency than memory cells. Neutrophils roll, but are not arrested by SLC, whereas they respond to immobilized IL-8 with rapid arrest. Thus, our artificial HEV system recapitulates critical features of lymphocyte interactions with HEV in vivo. These observations strongly point to the participation of SLC in homing of lymphocytes to secondary lymphoid organs.
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PMID:A high endothelial cell-derived chemokine induces rapid, efficient, and subset-selective arrest of rolling T lymphocytes on a reconstituted endothelial substrate. 983 23

Intraepidermal collections of neutrophils and lymphocytes are unique features of the inflammatory reaction of psoriasis. Migration of leukocytes from dermis to the epidermis suggests a role for chemotactic agent(s). In recent years, increased levels of chemokines such as IL-8 , GRO-a and MCP-1 have been reported in the keratinocytes of psoriatic tissue. IL-8 and GRO-alpha belong to a subfamily (C x C) class and MCP-1 is a beta chemokine. In this study, we investigated RANTES, which is a beta chemokine (C-C class); RANTES has been found to be associated with various cell-mediated hypersensitive disorders. We obtained eight skin biopsies from chronic psoriatic plaques, and five biopsies each from non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 microm cryosections and stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry techniques were applied. RANTES was detected only in the keratinocytes. The number of keratinocytes in per mm2 of epidermis stained for RANTES were 116.79+/-98.42 in psoriatic tissues compared to 32.00+/-46.05 (p<0.05), 6.39+/-3.59 (p<0.01), 2.64 +/-1.15 (p<0.01) and 3.53+/-5.26 (p<0.01), respectively, in the non-lesional, lichen planus, eczematous lesions and normal skin. This is the first study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related molecules (C x C class) are predominantly chemotactic for neutrophils and MCP-1 is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the activated T cells to the epidermis of the psoriatic lesions. In addition, RANTES activates T cells. These results suggest that RANTES may have a significant role in the inflammatory process of psoriasis. Our findings further substantiate a regulatory role for keratinocytes in the inflammatory process of psoriasis.
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PMID:Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic mechanism for psoriasis. 1008 50

H. pylori colonisation of the stomach causes the recruitment of the inflammatory cells by the adherence of the bacteria with the epithelium and the release of factors of virulence either to the contact (oipA or other soluble factors) or in the cell by translocation (CagA). Such contact triggers interleukin 8 expression in the epithelial cell and attracts lymphocytes and monocytes into the chorion. Bacterial lipopolysaccharide and urease support the activation of these inflammatory cells. The lymphocytes produce pro-inflammatory cytokines, which direct the immune response towards the Th1 pathway. The variability of the inflammatory response depends on hereditary factors of the host such as the interleukin 1 genotypes, which determine the level of the pro-inflammatory cytokine expression, and of bacterial factors such as the cag pathogenicity island, the lipopolysaccharide and the vacuolating toxin, vacA. The mucosal inflammation provokes apoptosis and atrophy of the epithelial cells through the effect of pro-inflammatory cytokines and free radicals. Epithelial proliferation is a consequence of excessive apoptosis caused by the infection. It is stimulated by the expression of inducible cyclo-oxygenase and inducible nitric oxide synthase. The development of atrophic gastritis towards cancer is supported by nitric oxide which has a mutagenic effect on DNA and inhibits p53 protein and by the bacterium itself which decreases DNA mismatch repairing activity. The gastritis induced by Helicobacter pylori changes acid secretion according to the prevalent location of the gastritis in the antrum or in the gastric body. Prevalent gastritis in the gastric body causes hypochlorhydria by reducing the release of histamin from ECL cells and inhibiting the parietal cells through the effect of tumor necrosis factor and interleukin 1-beta. Hypochlorhydria is more marked among patients having a pro-inflammatory genotype for interleukin 1-beta and those infected by bacteria with virulence factors. In the event of antrum predominant gastritis, the pro-inflammatory cytokines cause a reduction of somatostatin and gastrin releases from the D and the G cells, respectively. The result of all is increased maximal acid output and the meal-stimulated acid secretion.
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PMID:[What are the gastric modifications induced by acute and chronic Helicobacter pylori infection?]. 1270 Apr 95

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.
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PMID:Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer. 1465 87


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