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)

Interleukin-8 (IL-8) exhibits activities on bone marrow progenitor cells such as regulation of their growth and their mobilization into peripheral blood. In order to clarify the molecular mechanism of the effects of IL-8 on mouse bone marrow cells, we examined the cellular distribution of mouse IL-8 receptor homologue by an immunofluorescence analysis. Peripheral blood Gr-1+ mature granulocytes, and a substantial portion of NK1.1+ natural killer cells in peripheral blood and spleen were stained positively with anti-mouse IL-8 receptor homologue antibody, whereas CD4+, CD8+, or B220+ lymphocytes in peripheral blood and spleen, and thymocytes were not. Moreover, a small portion of ER-MP20+ monocytes in peripheral blood but neither peritoneal resident nor bone marrow macrophages were stained with anti-IL-8 receptor homologue antibody. In bone marrow, mature granulocytes and to a lesser degree, metamyelocytes and myelocytes expressed IL-8 receptor homologue. Moreover, lineage marker (Lin)-c-kit+ bone marrow progenitor cells started to express IL-8 receptor homologue only 5 days after in vitro culture with IL-3 and stem cell factor when metamyelocytes and myelocytes appeared. These results indicated that myeloid lineage cells express a substantial number of IL-8 receptor homologues only at the stage of myelocytes.
 ...
PMID:Detection of mouse IL-8 receptor homologue expression on peripheral blood leukocytes and mature myeloid lineage cells in bone marrow. 883 Jul 94

Cell priming and stimulation of different cytokines (which include chemokines and growth factors) are typical features of human basophils. Recently, it has been shown that the macrophage chemotactic protein-1 (MCP-1), RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent direct secretagogues for human basophils and that interleukin-3 (IL-3), IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are priming factors for subsequent potentiation of mediator release from basophils induced by different stimuli. This observation may be clinically important for the activation and recruitment of inflammatory cells in different immune responses of the skin (e.g. late-phase reactions). The aim of the present study was to investigate whether cytokines and chemokines are also capable of priming or stimulating isolated human skin mast cells (SMC). SMC were either stimulated directly with the cytokines alone or preincubated with these factors for 10 min before being activated with suboptimal concentrations of anti-IgE, A23187 or substance P. IL-3, IL-5, GM-CSF, platelet factor-4 (PF-4), IL-8, MCP-1 and MIP-1 alpha (each at concentrations of 1 ng/ml to 1 microgram/ml, log steps) did not significantly modulate histamine release from SMC induced by the three different secretagogues. RANTES exhibited a weak but significant potentiating effect on IgE-mediated activation. Stem cell factor (SCF) as a positive control was able to prime mast cell histamine release strongly. In addition, PF-4, MCP-1, RANTES and MIP-1 alpha were incapable of inducing direct histamine release from SMC. In experiments with isolated human peripheral basophils, however, we observed potent Fc epsilon RI-mediated priming effects evoked through IL-3, IL-5 and GM-CSF. We conclude that SMC derived from healthy donors are not targets of (immuno)modulatory factors that prime or stimulate basophils.
 ...
PMID:Effects of basophil-priming and stimulating cytokines on histamine release from isolated human skin mast cells. 884 26

We have demonstrated previously that a single bolus-injection of interleukin (IL)-8 induces instant mobilization of hematopoietic progenitor cells (HPC) in mice and primates. To further improve the mobilization of HPC, we treated mice with hematopoietic growth factors (HGF) before IL-8-administration. The mobilized HPC were transplanted into lethally irradiated recipient mice to study the effects on survival. Male donor mice (age 8-12 weeks, weight 20-25 grams) were pretreated intraperitoneally (ip) with a fixed dose of 2.5 micrograms of either granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, stem cell factor (SCF), or saline administered twice daily for 2 to 4 days. Then a fixed dose of 30 micrograms of IL-8 was administered ip at various time intervals before harvesting blood, bone marrow, and spleen. Cell counts and numbers of colony-forming units granulocyte/macrophage (CFU-GM) of these organs were assessed. Donor mice pretreated with HGF for 2 days and subsequently injected with IL-8 showed an increase in the numbers of circulating CFU-GM per mL blood from 168 +/- 98 to 402 +/- 201 (mean +/- SD, CFU-GM/mL blood) when GM-CSF was used, 314 +/- 133 to 2502 +/- 513 with G-CSF, and 27 +/- 15 to 524 +/- 339 with SCF compared with saline-pretreated controls (28 +/- 17 to 462 +/- 335 CFU-GM/mL blood, mean +/- SD; n = 42 and 40 per interval). Donor-mice pretreated for 4 days with IL-3 or GM-CSF showed an increase in the numbers of circulating HPC from 62 +/- 52 to 368 +/- 118 and 859 +/- 387 to 1034 +/- 421, respectively (CFU-GM/mL, mean +/- SD, n = 4 per group). Lethally irradiated (8.5 Gy) female Balb/c mice were then injected with decreasing numbers of peripheral blood mononuclear cells (PBMNC). Transplantation of 1.5 x 10(5) MNC obtained from donors pretreated with SCF for 2 days prior to IL-8 mobilization resulted in a significantly enhanced survival of 100% of the recipients, whereas recipients of PBM-NCs derived from donors treated with SCF only or IL-8 as a single injection had a survival rate at day 60 of only 50% and 60% respectively. When equal numbers of IL-8 mobilized MNCs from G-CSF, GM-CSF, or IL-3 pretreated donors were transplanted into lethally irradiated recipients, no such survival-advantage was observed. We conclude that pretreatment with SCF for 2 days improves the mobilizing effect induced by IL-8 and that transplantation of these cells enhances survival of lethally irradiated recipients.
 ...
PMID:Improved survival of lethally irradiated recipient mice transplanted with circulating progenitor cells mobilized by IL-8 after pretreatment with stem cell factor. 891 84

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that of myoid cells found in adult and fetal human bone marrow cords. We studied the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different bone marrow samples. RT-PCR indicated that 30 cytokines (out of 42 studied) were expressed by CDCLs (20 after medium renewal and hydrocortisone renewal, three after addition of interleukin I beta (IL-1 beta) and seven in only part of the CDCL layers examined). The cytokines expressed comprised mediators known to be involved in the maintenance of early and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, IL-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoietin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, tumor necrosis factor alpha, leukemia inhibitory factor, transforming growth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascular endothelial growth factor) and mediators whose usual target (and source) is the connective tissue-forming cells (platelet-derived growth factor A, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neuronal cells (nerve growth factor). The cytokines not expressed were lymphokines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon gamma) or mediators synthesized by macrophages (inhibin, activin, platelet-derived growth factor B, and IL-1 receptor antagonist). This study complements the description of the phenotype of the myoid cells, confirming that these cells are the marrow connective tissue-forming cells; moreover, this work suggests that stromal control of hematopoiesis is multifactorial and that myoid cells are involved in the control of marrow angiogenesis and innervation.
 ...
PMID:The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. 909 Jul 90

Inflammatory cells infiltrate the liver in response to microbial infection or hepatic injury. To assess the potential role hepatocytes may play in initiating or amplifying the acute inflammatory response in the liver, we used three human hepatocyte cell lines and primary human hepatocyte cultures to characterize the repertoire of cytokines that can be expressed and regulated in hepatocytes in response to agonist stimulation or bacterial infection. As reported herein, a proinflammatory cytokine gene program that includes C-X-C and C-C chemokines [interleukin-8(IL-8), growth related (GRO)-alpha, GRO-beta, GRO-gamma, epithelial neutrophil activating peptide-78 (ENA-78), and RANTES] and the cytokines tumor necrosis factor-alpha (TNF-alpha) and macrophage colony stimulating factor was upregulated in human hepatocytes after stimulation with IL-1 alpha or TNF-alpha or bacterial invasion. In contrast, expression of hematopoietic/ lymphoid growth factors by the same cells was either down-regulated (erythropoietin and stem cell factor) or unchanged (IL-7 and IL-15) in response to the identical stimuli. Hepatocytes did not express cytokines that often are associated with the regulation of antigen-specific immune responses (IL-2, IL-4, IL-5, IL-10, IL-12p40, IL-13, and interferon-gamma) or genes for several other proinflammatory cytokines [IL-1 alpha, IL-6, monocyte chemotactic protein-1 (MCP-1), and MCP-3] or hematopoietic growth factors (granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-3, and IL-11). Together, these studies suggest that hepatocytes can both initiate and amplify acute inflammatory responses in the liver through the regulated expression and secretion of a specific array of proinflammatory cytokines.
 ...
PMID:Human hepatocytes express an array of proinflammatory cytokines after agonist stimulation or bacterial invasion. 927 10

The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin-Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on beta1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1alpha, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-beta1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that beta1-integrin-mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of beta1-integrins in hematopoietic progenitor cells.
 ...
PMID:Adhesion and migration are differentially regulated in hematopoietic progenitor cells by cytokines and extracellular matrix. 934 36

The human bladder carcinoma cell line KU-19-19 synthesizes and secretes hematopoietic growth factors. Conditioned medium (CM) from KU-19-19 stimulated the [3H]thymidine incorporation of growth factor-dependent hematopoietic cell lines. ELISA documented high amounts of granulocyte colony-stimulating factor (G-CSF; > 5 ng/ml); also granulocyte-macrophage CSF (GM-CSF), macrophage-CSF (M-CSF), stem cell factor (SCF), IL-6, and IL-8 were detected in KU-19-19 CM. Pretreatment with phorbol ester, IL-1 beta, or IFN-gamma increased the level of G-CSF, GM-CSF, and M-CSF in KU-19-19 CM. Thus, KU-19-19 represents a reliable source for purification of G-CSF and can easily be used to support proliferation of growth factor-dependent cell lines. The ability to respond to different stimuli suggests that several regulatory pathways may be involved in cytokine production of this bladder carcinoma cell line.
 ...
PMID:Bladder carcinoma cell line KU-19-19-derived cytokines support proliferation of growth factor-dependent hematopoietic cell lines: modulation by phorbol ester, interferon-gamma and interleukin-1 beta. 946 44

By using a specific enzyme-linked immunosorbent assay, the authors demonstrated that human bone marrow stromal cells produce IL-6 and IL-8. Their synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). Interleukin 6 (IL-6) and IL-8 production in response to PMA were markedly diminished by the PKC inhibitor staurosporine. IL-6 (10 ng/ml) stimulated IL-8 production with 0% and 10% fetal calf serum (FCS) in the culture medium. In similar conditions, IL-8 (10 ng/ml) enhanced IL-6 production. IL-1 alpha, IL-1 beta, and IL-3, tumour necrosis factor alpha (TNF-alpha), Stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (at 10 ng/ml) stimulated IL-6 and IL-8 production in 0% and 10% FCS. G-CSF stimulated and IL-4 inhibited IL-8 production in 10% FCS. IL-2, IL-4 and bFGF stimulated IL-6 production in 0% FCS. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of IL-6 and IL-8 inside human bone marrow.
 ...
PMID:IL-6 and IL-8 production by human bone marrow stromal cells. 951 98

In recent years there has been an explosive expansion of knowledge relating to a family of proteins involved in the intercellular communication network of the immune system. These substances, referred to as cytokines, are importantly involved in the highly regulated complex sequence of events of cellular interaction that comprise immune responses. Atopic diseases, which afflict 20-30% of the general population, are now considered to be associated with a set of abnormal genetically regulated immune responses to foreign antigens, i.e., allergens. The atopic individuals is characterized by the excessive production of IgE antibody to allergens after inhalation, ingestion, and surface contact. There are now recognized over 19 major classes of cytokines, which have been organized into the following categories according to their major functional activities: 1) Acute phase reactants, promoting and mediating natural immunity (e.g., IL-1, IL-6, TNF, interferons alpha and beta, and IL-8); 2) Cytokines that mediate cellular growth and differentiation (e.g., IL-7, IL-4, IL-2, IL-5, IL-10, IL-12, IL-13); 3) Cytokines that act as hematopoietic growth factors (IL-3, GMCSF, IL-9, IL-11, stem cell factor); 4) Chemokines (alpha and beta major groups, DTG, RANTES); and 5) Cytokines that exert lymphocyte regulatory activity (EG, IFN-gamma, TGF). Of particular importance to allergic disease is the recent recognition of the regulation of helper immune function by two lineages of T helper cells, i.e., Th1 and Th2, by these cytokines. The Th2 hypothesis of allergy (4) considers atopy as a Th2-driven hypersensitivity reaction to allergens of complex genetic and environmental origins, in which the Th1 lineage, normally driven by IL-2, TNF, and IFN-gamma is deficient, and in which a predominant Th2 response is seen that is driven by IL-4, IL-13, IL-5, and IL-10. This knowledge is finding application in both the diagnosis and therapy of allergic diseases, through the measurement or use of cytokines, which may replace deficient quantities, or the use of anticytokines, which may neutralize elevated quantities of cytokines, events that collectively contribute to the immunologic imbalance characteristic of the allergic state. In the future, the application of cytokines will continue to find clinical application in allergic disease, and it behooves the clinical allergist-immunologist to keep abreast of the exciting new developments that are occurring in this field.
 ...
PMID:Cytokines and allergic diseases: clinical aspects. 987 71

The mechanism(s) underlying the release of stem/progenitor cells from bone marrow into the circulation is poorly understood. We hypothesized that matrix metalloproteinases (MMPs), especially gelatinases, which are believed to participate in the proteolysis of basement membranes and in the migration of leukocytes, may facilitate this process. First, we investigated whether CD34(+) stem/progenitor cells express gelatinases A (MMP-2) and/or B (MMP-9) and whether growth factors and cytokines (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], stem cell factor [SCF], macrophage colony-stimulating factor [M-CSF], interleukin-3 [IL-3], IL-6, IL-8, and tumor necrosis factor-alpha [TNF-alpha]) are able to modulate their expression. Next, we examined the transmigration of these stem/progenitor cells through reconstituted basement membrane (Matrigel) and its modulation by growth factors and cytokines. CD34(+) cells were obtained from steady-state bone marrow and peripheral blood (from leukapheresis products collected either in steady-state hematopoiesis or after mobilization with G-CSF plus chemotherapy or G-CSF alone). We found that peripheral blood CD34(+) cells, regardless of whether they were mobilized or not, strongly expressed both gelatinases (MMP-2 and MMP-9) in contrast to steady-state bone marrow CD34(+) cells, which did not. However, all the growth factors and cytokines tested could induce MMP-2 and MMP-9 secretion by the latter cells. Moreover, the stimulatory effects of G-CSF and SCF on both MMP-2 and MMP-9 secretion were found to be significantly higher in CD34(+) cells isolated from bone marrow than in those from peripheral blood. In addition TNF-alpha, GM-CSF, and IL-6 increased the secretion of a partially active form of MMP-2. Basal transmigration of bone marrow CD34(+) cells through Matrigel was lower than that of peripheral blood CD34(+) cells (P <.0001), but growth factors and cytokines increased it by 50% to 150%. Positive correlations were established between expression of gelatinases and CD34(+) cell migration (r >.9). The stimulatory effect of G-CSF was significantly greater on the migration of CD34(+) cells from bone marrow than on those from peripheral blood (P =.004). Moreover, CD34(+) cell migration was reduced to approximately 50% by antibodies to MMP-2 and MMP-9, tissue inhibitors of metalloproteinases (rhTIMP-1 and -2), and o-phenanthroline. TNF-alpha-induced gelatinase secretion and migration of CD34(+) cells and of clonogenic progenitors (colony-forming unit-granulocyte-macrophage [CFU-GM], burst-forming unit-erythroid [BFU-E], colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM], and colony-forming unit-megakaryocyte [CFU-MK]) were dose-dependent. Therefore, this study demonstrated that CD34(+) cells that are circulating in peripheral blood express both MMP-2 and MMP-9 and transmigrate through Matrigel. In contrast, CD34(+) cells from steady-state bone marrow acquire similar properties after exposure to growth factors and cytokines, which upregulate expression of gelatinases and transmigration of these cells when they enter the bloodstream. Hence, we suggest that growth factors and cytokines induce release of stem/progenitor cells from bone marrow into peripheral blood during mobilization, as well as during steady-state hematopoiesis, by signaling through gelatinase pathways.
 ...
PMID:Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. 1023 90


<< Previous 1 2 3 4 5 6 7 Next >>