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)

Bone marrow stromal cells regulate marrow haematopoiesis by secreting interleukins (IL) such as IL-8. Lipid mediators modulate IL-8 synthesis in numerous cell types. We have investigated the effects of 5 lipid mediators (PAF, PGE(2), LTB(4), 12-HETE and 15-HETE) on the spontaneous and cytokine-induced IL-8 synthesis by human bone marrow stromal cells. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts. By using a specific ELISA, we found that the production of IL-8 by marrow stromal cells is enhanced after stimulation with 12-HETE (1 microM) both in serum-free and serum-containing culture medium. LTB(4)(1 microM) enhances IL-8 production only in serum-supplemented medium. PAF, PGE(2)and 15-HETE (1 microM to 0.1 nM) have no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stromal cells. PGE(2)(1 microM or 10 nM) reduces marrow stromal cell IL-8 synthesis in response to IL-1alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-HETE and LTB(4)have no effect. In conclusion, various lipid mediators modulate the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in the regulation of IL-8 production within the human bone marrow.
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PMID:Lipid mediators modulate the synthesis of interleukin 8 by human bone marrow stromal cells. 1043 8

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.
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PMID:Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities. 1060 Aug 85

Activation of the kallikrein-kinin system in lung injury has long been recognized. However, the effects of bradykinin (BK) on human lung fibroblasts (HLF) remain to be elucidated. We determined whether BK stimulates HLF to release chemotactic activity for neutrophils and monocytes (NCA and MCA, respectively). We evaluated HLF supernatant fluids for chemotactic activity through a blind-well chamber technique. HLF released NCA and MCA in a dose- and time-dependent manner in response to BK. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by a leukotriene (LT) B(4) receptor antagonist and by antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF). MCA was attenuated by the LTB(4) receptor antagonist and by antibodies to monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-beta. Both the LTB(4) receptor antagonist and these antibodies inhibited chemotactic activity of the molecular weights corresponding to MCP-1, GM-CSF, and TGF-beta, separated by column chromatography. The concentrations of IL-8, G-CSF, MCP-1, GM-CSF, and TGF-beta in supernatant fluids increased significantly in a time-dependent manner in response to BK. The receptors responsible for the release of NCA, MCA, and individual chemokines included both BKB(1) and BKB(2) receptors. These data suggest that BK may stimulate lung fibroblasts to release inflammatory cytokines, which may modulate lung inflammation.
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PMID:Bradykinin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity. 1061 68

Volatile organic compounds (VOCs) have been implicated as causative agents in asthma and building-related illness. To determine whether a mixture of VOCs could impair lung function or cause airway inflammation among subjects without bronchial hyperresponsiveness, the authors conducted a randomized, crossover-design trial of controlled human exposures to filtered air for four hours, VOCs at 25 mg/m(3) for four hours, and VOCs at 50 mg/m(3) for four hours, using a VOC mixture based on sampling of indoor environments. VOC exposures caused dose-related increases in lower respiratory, upper respiratory, and non-respiratory symptoms, with no significant change in lung function (FEV(1);, FVC, or FEF(25-75), nasal lavage cellularity or differential cell counts, induced sputum cellularity or differential cell counts, or biomarkers of airway inflammation, including IL-8, LTB(4), or albumin in nasal lavage or induced sputum samples. Atopic individuals had significantly reduced FEE(25-75 following exposure to VOCs at 50 mg/m(3), suggesting that these individuals may be more sensitive to the health effects of VOCs. The authors conclude that reductions in levels of VOCs to substantially less than 25 mg/m(3) are required if a "non-irritating" work environment is desired.
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PMID:The respiratory effects of volatile organic compounds. 1063 31

Contact lens wear has been associated with an increased risk of corneal infection and/or inflammation. We studied the hypothesis that contact lens wear alters the number of polymorphonuclear leukocytes (PMNs) on the cornea during sleep and the levels of inflammatory mediators in the tear film. Three groups of subjects were analysed: a non-contact lens wearing group (NCLW), non-adapted (neophyte) contact lens wearers (NACLW) who wore lenses during sleep for the first time in this study and adapted contact lens wearers (ACLW) who normally wore lenses on a daily wear schedule. Ocular PMNs were collected by a non-contact irrigation technique and their numbers counted after staining. Tears were collected from each group and analysed using ELISAs for the presence of the PMN chemoattractants IL-8 and LTB(4)and the cytokines IL-1beta, IL-6 and GM-CSF. Corneal irrigation data demonstrated significantly higher numbers of PMNs from NACLW (P<0.05) compared to the other groups. ACLW showed significantly fewer PMNs (P =0.03) compared to NCLW group. The NACLW group had significantly lower concentrations (P<0. 05) of IL-8, LTB(4)and IL-6 in their tears after 8 hr of sleep compared to the other groups. The ACLW group had significantly (P<0. 05) higher levels of IL-8 at most time points compared to the other two groups. The levels of the chemoattractants IL-8 and LTB(4)in tears were inversely related to the numbers of PMNs from the corneal surface and the chemotaxis of PMNs in vitro. During one night sleep in contact lenses the numbers of PMNs and the concentration of certain inflammatory mediators are significantly altered compared to no lens wear. However, this alteration changes from NACLW to ACLW. This may have effects on the ability of the eye to defend itself during contact lens wear.
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PMID:Contact lens wear alters the production of certain inflammatory mediators in tears. 1071 11

Although neutrophil migration from the systemic circulation involves the beta2- (or CD18) integrin family, the existence of an alternative, CD18-independent route of neutrophil extravasation to tissues has been demonstrated in animal models. The molecular interactions involved in this alternative migratory route have not yet been characterized. The objective of this study was to assess the CD18-dependency of neutrophil migration across human endothelial cells from an organ known to support CD18-independent migration, the lung, with a view to establishing an in vitro model to facilitate study of CD18-independent migration. Neutrophil migration across human pulmonary artery endothelial cells (HPAECs) in response to three different chemoattractants, formylmethionyl leucylphenyl-alanine (FMLP), interleukin (IL)-8, and leukotriene (LT) B(4), was examined. Results demonstrated that a function-blocking antibody to CD18 decreased FMLP-stimulated migration by 71.7 +/- 4.4% (P < 0.001). In contrast, migration in response to LTB(4) was decreased by only 20.5 +/- 10.2% (P < 0.01), and no significant decrease was observed with migration to IL-8. Neutrophils that migrated to FMLP had 1.7-fold more surface CD11b/CD18 compared with nonmigrated neutrophils (P < 0.01), whereas this integrin complex was not significantly upregulated on neutrophils that had migrated to IL-8 or LTB(4). Further investigation of this migratory route indicated that it did not involve the beta1 integrins (CD29) or the endothelial selectins, E- or P-selectin, nor did it require the activity of either metalloproteinases or neutrophil elastase. These results indicate that neutrophil migration across HPAECs in vitro to IL-8 and LTB(4) is predominantly CD18-independent and provides a much-needed in vitro system for examination of the neutrophil-endothelial interactions involved in this alternative migratory route.
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PMID:Interleukin-8 and leukotriene-B(4), but not formylmethionyl leucylphenylalanine, stimulate CD18-independent migration of neutrophils across human pulmonary endothelial cells in vitro. 1091 80

Selected host defense functions of neutrophils isolated from American bison (Bison bison) were characterized and compared with those of cattle (Bos taurus). Bison neutrophils had a robust chemotactic response to both IL-8 and LTB(4), with maximal responses occurring at 10(-7) M (IL-8) and 10(-8) M (LTB(4)). The magnitude of the chemotactic response to IL-8 was similar in bison and bovine neutrophils (except at 10(-7) M IL-8, where bison had a stronger response). In response to LTB(4), bison neutrophils had a much stronger chemotaxis at both 10(-8) and 10(-7) M than did bovine cells. Production of reactive oxygen species (ROS) in response to phorbol myristate acetate (PMA) and opsonized zymosan (OpZ) was similar between bison and bovine neutrophils. However, the production of ROS in bison neutrophils stimulated with OpZ was primarily intracellular, while extracellular release of ROS was evident in bovine neutrophils stimulated with OpZ. Like bovine neutrophils, bison neutrophils did not generate a respiratory burst in response to fMLF. Granules prepared from bison neutrophils had potent direct killing action on the Gram-negative bacteria Escherichia coli but failed to kill the Gram-positive bacteria Staphylococcus aureus and, at intermediate doses, actually had a permissive effect for this bacteria. Thus, bison neutrophils have potent host defense capabilities similar in quality to those of bovine neutrophils; however, unique differences are present, which may allow bison neutrophils to respond to the distinct immunological challenges that bison encounter.
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PMID:Host defense function in neutrophils from the American bison (Bison bison). 1106 90

Stimulation of vascular endothelial cells by tumor necrosis factor alpha (TNFalpha) plays a critical role in the pathogenesis of inflammation and vascular diseases. Changes in the gene expression profile in cultured human umbilical vein endothelial cells (HUVEC) treated with TNFalpha was analyzed with high-density oligonucleotide arrays comprised of 35,000 genes. TNFalpha stimulation profoundly induced genes involved in signal transduction, leukocyte adhesion and chemoattraction. ICAM-1 mRNA (fold change 111.9) was most profoundly induced followed by TNFalpha receptor-associated factor 1 (TRAF1) (95.5), Bcl3 (71.8), IL8 (65.4), fractalkaine (62.4), E-selectin (48.0), lymphotoxin beta (41.3) and VCAM-1 (31.7). In addition to these previously known genes, 18 poorly characterized or novel genes known as ESTs profoundly induced by TNFalpha. Initial sequencing analysis identified three of these the genes for squalene epoxydase, chromodomain helicase DNA binding protein 4, and CLP respectively. Further analysis of these genes will provide important information about TNFalpha signaling and function in vascular endothelial cells.
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PMID:The gene expression profile of human umbilical vein endothelial cells stimulated by tumor necrosis factor alpha using DNA microarray analysis. 1142 43

This study sought to determine whether vascular endothelial growth factor (VEGF)-induced permeabilisation of pulmonary endothelium to macromolecules could be related to a permissive role for neutrophil-derived VEGF in neutrophil transmigration. Treatment of human pulmonary artery endothelial cell (HPAEC) monolayers with 1, 10 or 100 ng/ml VEGF for 15 min or 1, 10 ng/ml for 90 min significantly increased endothelial permeability to trypan blue-labelled albumin (TB-BSA). These increases were correlated with changes in the cellular distribution of F-actin, as visualised by rhodamine-phalloidin staining: increased stress fibre formation, cellular elongation and formation of intercellular gaps after 15 min; at 90 min, there was also evidence of microspike formation and extension of spindle processes from the cell surface. Treatment of human neutrophil suspensions with 200 nM phorbol myristyl acetate (PMA), n-formyl-methionyl leucylphenylalanine (fMLP, 10 nM), interleukin-8 (IL-8, 10 nM) (but not with leukotriene B(4) (LTB(4)) 100 nM), for 30 min caused significant extracellular release of neutrophil VEGF stores. A permissive role for neutrophil-derived VEGF in facilitating migration across HPAEC monolayers was assessed in experiments using a functional blocking antihuman VEGF antibody. In the presence of this antibody (10 microg/ml), neutrophil migration in response to fMLP (10 nM), IL-8 (10 nM) or LTB(4) (100 nM) was not significantly different to that in the absence of antibody. We conclude that neutrophil-derived VEGF does not play a functional role in facilitating neutrophil migration across pulmonary vascular endothelium, despite its ability to induce cytoskeletal changes and enhance endothelial macromolecular permeability.
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PMID:Investigation of vascular endothelial growth factor effects on pulmonary endothelial monolayer permeability and neutrophil transmigration. 1174 37

The present study examines the influence of kinins on the migratory capacity of human polymorphonuclear leukocytes under in vitro conditions using the Boyden chamber technique. By means of checkerboard analysis the migration of neutrophils induced by bradykinin could be characterized as true chemotaxis. The stimulation of human neutrophils with bradykinin, with the nonpeptide B(2) receptor agonist FR190997 as well as with des-Arg(9)-bradykinin and des-Arg(10)-kallidin results in a concentration-dependent migration. Pretreatment of the neutrophils with the B(2) receptor antagonist HOE-140 (icatibant) inhibited the bradykinin-induced migration but not that induced by B(1) receptor agonists, whereas the B(1 )receptor antagonist des-Arg(10)HOE-140 abolished the migration elicited by des-Arg(9)-bradykinin or des-Arg(10)-kallidin but not that evoked by bradykinin. Pretreatment of the neutrophils with the leukotriene B(4) (LTB(4)) antagonist ZK158252 inhibited the LTB(4)-induced chemotaxis as well as the chemotaxis produced by bradykinin and des-Arg(10)-kallidin. An involvement of interleukin-1beta and of the chemokine IL-8 in the bradykinin-induced migration in vitro could be excluded during the migration time of the neutrophils. In conclusion, the present study provides pharmacological evidence showing that B(1) and B(2) kinin receptors are involved in the migration of human neutrophils in vitro, that LTB(4) participates in the downstream pathway and that the B(1) kinin receptor seems to be expressed already under physiological conditions.
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PMID:Migratory responses of polymorphonuclear leukocytes to kinin peptides. 1237 5


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