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 interleukin-12 receptor (IL-12R)beta1 chain is an essential component of the functional IL-12R on both human T and natural killer cells. In this report it is shown that activation of human peripheral blood mononuclear cells (PBMC) with anti-CD3 monoclonal antibody (mAb) or phytohemagglutinin resulted in the up-regulation of IL-12Rbeta1 expression and IL-12 binding. Kinetic studies revealed that maximum expression of IL-12Rbeta1 and IL-12 binding occurred on days 3-4. Anti-CD3-induced expression of IL-12Rbeta1 chain and IL-12 binding by PBMC was augmented by anti-CD28 mAb, indicating that the potentiating effect of anti-CD28 on T cell responses to IL-12 could be mediated, at least in part, by the enhancement of IL-12R expression. Among 16 cytokines tested, IL-2, IL-7 and IL-15 markedly induced IL-12Rbeta1 expression and IL-12 binding on resting PBMC, whereas IL-1alpha and tumor necrosis factor-alpha had a minimal enhancing effect. In contrast, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-alpha, IFN-gamma, granulocyte/macrophage colony-stimulating factor and transforming growth factor (TGF)-beta2 had no detectable enhancing effect. Anti-CD3-induced expression of IL-12Rbeta1 and of low-affinity IL-12 binding sites was partially inhibited by TGF-beta2, IL-10 and IL-4; however, TGF-beta2 and IL-10 completely abolished anti-CD3-induced expression of high-affinity IL-12 binding sites. Consistent with the reduction of high affinity IL-12 binding sites, PBMC activated with anti-CD3 mAb in the presence of TGF-beta2 or IL-10 failed to produce IFN-gamma or to proliferate in response to IL-12. These results suggest that Th2 cell-derived cytokines can inhibit IL-12-induced biological functions by inhibiting IL-12R expression and that expression of a second subunit of the IL-12R (IL-12Rbeta2), required for the formation of high-affinity IL-12 binding sites, may be more highly regulated by TGF-beta2 and IL-10 than is expression of IL-12Rbeta1.
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PMID:Regulation of interleukin-12 receptor beta1 chain expression and interleukin-12 binding by human peripheral blood mononuclear cells. 902 11

Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-1, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC-1 cells secreted IL-4, IL-8, and GM-CSF protein after activation and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membranes purified from activated T cells to mast cell cultures induced transcripts selectively for IL-8 and none for other proinflammatory cytokines. Flow cytometry revealed that resting HMC-1 cells express CD40, a molecule involved in contact-dependent signaling of monocytes and B cells by T cells. However, activation of HMC-1 by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demonstrates that human mast cells are capable of expressing multiple cytokines that can be inhibited by glucocorticoids. It also raises the possibility that T cells may activate mast cell cytokine synthesis by novel contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.
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PMID:Multifunctional cytokine expression by human mast cells: regulation by T cell membrane contact and glucocorticoids. 908 42

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.
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PMID:The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. 909 Jul 90

Migration of eosinophils through the basement membrane barrier is an important step for their infiltration into tissues. To investigate the mechanism of transmigration, we used a chamber fitted with a Matrigel membrane as a model of the basement membrane. In this model, eosinophils treated with cytokines or chemotactic factors alone did not transmigrate from the upper to the lower chamber. However, platelet-activating factor (PAF) strongly induced transmigration of eosinophils stimulated by interleukin (IL)-5, indicating that both a cytokine and a chemotactic factor are required for eosinophil migration through Matrigel. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 also stimulated eosinophil transmigration in the presence of PAF. Of seven eosinophil chemotactic factors tested, leukotriene B4, C5a, RANTES, macrophage inflammatory protein-1alpha, and IL-8 did not induce significant eosinophil transmigration. Only PAF and eotaxin induced transmigration of eosinophils through Matrigel in the presence of IL-5; PAF was more potent than eotaxin at the optimal concentration. In contrast, PAF, eotaxin, and RANTES all potently induced migration of eosinophils through bare membrane in the absence of IL-5. Finally, eosinophil migration through Matrigel was markedly reduced by a combination of anti-CD18 and anti-CD29 monoclonal antibodies, suggesting that it is mediated by beta1- and beta2-integrin adhesion molecules. Our findings demonstrate that eosinophil transmigration through a basement membrane model requires both a specific chemoattractant, such as PAF, and an eosinophil-activating cytokine, such as IL-5. This synergistic effect is likely important in the tissue accumulation of activated eosinophils in allergic and other eosinophil-associated diseases.
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PMID:Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines. 911 57

To evaluate whether concentrations of cytokines supposed to be involved in eosinophil recruitment and activation were elevated in cystic fibrosis (CF), we assessed interleukin-3 (IL-3), IL-5, IL-8, regulated on activation, normal T-cell expressed and secreted (RANTES); and granulocyte-macrophage colony stimulating factor (GM-CSF) in sputa from 32 patients with CF, eight patients with atopic bronchial asthma, and six patients with bacterial pneumonia. In addition, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as markers of eosinophil activation. In patients with CF, sputum levels of IL-8 were elevated (p < 0.01) as compared with asthmatic patients. Concentrations of IL-3, ECP, and EPX were not different in the two groups. However, IL-5 (p < 0.0001), RANTES (p < 0.003), and GM-CSF (p < 0.0001) were significantly lower in the CF group than in subjects with asthma. IL-5 was detected only in sputum samples from CF patients with Aspergillus sensitization. In patients with pneumonia, IL-8 levels only were increased. In CF sputum, ECP levels were significantly correlated with the levels of IL-8 (r = 0.626, p < 0.0001) and IL-3 (r = 0.642; p < 0.0001), whereas in asthmatic patients IL-5, IL-8, and RANTES concentrations were significantly related to ECP in sputum. These findings suggest that different cytokine profiles are responsible for eosinophil activation in patients with CF as compared with asthmatic patients. In CF, IL-8 and IL-3 appear to be responsible for increased degranulation of eosinophils.
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PMID:Cytokine concentrations in sputum from patients with cystic fibrosis and their relation to eosinophil activity. 911 85

Interleukin 1-beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was determined in knee synovium of 16 patients with rheumatoid arthritis (RA) and 16 patients with seronegative spondyloarthropathies (SSP), by using polymerase chain reaction (PCR) amplification. The pattern of cytokines observed in RA synovium is of the macrophage-fibroblast type, with the highest expression of IL-1 beta and TGF-beta. GM-CSF and IL-2 bands were visualized in a minority of patients. Neither IL-4 nor IL-5 could be detected. No significant differences were observed in the cytokine profile between patients with early (< 12 months) and more advanced disease. No differences were observed according to gender, age, rheumatoid factor status and the duration of knee synovitis. The pattern of cytokines in the synovium of SSP patients is similar to that observed in RA patients and does not change in relation to disease duration. IL-2 was the only T-cell cytokine observed. These data provide evidence that the macrophage-fibroblast cells have an important role in early and more advanced rheumatoid synovitis, and show that this is also true for SSP peripheral synovitis.
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PMID:Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies. 911 72

Recent studies have identified eosinophils as a cellular of various cytokines, indicating that eosinophils play not only an effector role but also a regulatory role within the allergic inflammatory cell network. Because eosinophilopoietic factors are known to stimulate various functions of eosinophils, we examined the effect of interleukin (IL)-5 on chemoattractant-induced IL-8 generation from eosinophils. Although IL-5 alone induced little or no IL-8 production from eosinophils, short-term preincubation with IL-5 markedly enhanced the eosinophil IL-8 generation caused by C5a plus cytochalasin B (CB). IL-3 also potentiated C5a-induced IL-8 generation. Both factors were active at picomolar concentrations. Furthermore, competitive polymerase chain reaction (PCR) experiments revealed that the enhancement occurred at the pretranslational level. Since eosinophils in allergic inflammation are believed to be activated by these eosinophilopoietic factors, eosinophil-derived cytokines may play more important roles in the allergic inflammatory cell network than has been previously supposed.
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PMID:Eosinophilopoietic factors prime eosinophils for increased interleukin-8 generation. 914 May 23

Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Inflammatory cytokines can be divided into two groups: those involved in acute inflammation and those responsible for chronic inflammation. This review describes the role played in acute inflammation by IL-1, TNF-alpha, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. It also describes the involvement of cytokines in chronic inflammation. This latter group can be subdivided into cytokines mediating humoral responses such as IL-4, IL-5, IL-6, IL-7, and IL-13, and those mediating cellular responses such as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth factor-beta, and tumor necrosis factor alpha and beta. Some cytokines, such as IL-1, significantly contribute to both acute and chronic inflammation. This review also summarizes features of the cell-surface receptors that mediate the inflammatory effects of the described cytokines.
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PMID:Cytokines in acute and chronic inflammation. 915 5

In the last decade, new information was achieved on mast cells (MC). Their origin is assumed to be different from that of the basophils. There are two types of MC with differences in structure, distribution and function: conjunctival and mucosal. MCs are among the most important cells in the development of allergic inflammation through the cytokines and mediators released on the activation of the surface receptors (high-affinity receptors for IgE: Fc epsilon R1). The cytokines released by MCs, e.g., interleukin 5 (IL5), IL8, are chemoattractants for eosinophils and neutrophils, respectively. The two types of mediators released by MC-those preformed, such as histamine, tryptase, serotonin, and the newly-synthetized ones, such as prostaglandin D2 (PGD2), leukotrienes C4 (LTD4), D4 (LTD4), E4 (LTE4), induce vasodilatation, bronchoconstriction, cellular chemotaxis, increase vascular permeability. The involvement of MC in many human diseases was shown within in vivo and in vitro studies (in allergy, lung fibrosis, atherosclerosis, carcinogenesis, etc.).
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PMID:Mast cells as potent inflammatory cells. 916 16

Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of cellular and fluid-phase markers of airway inflammation. We investigated the extent to which DTT treatment influences these measurements as compared with phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from 20 asthmatic subjects, was examined within 2 h. All portions which looked more solid (less fluid) than saliva were collected from the expectorate. The selected sputum was then divided into two portions: one treated with one volume of DTT and one volume of PBS, the other with two volumes of PBS. The filtrates were assessed blind for total and differential cell count, viability, and fluid-phase eosinophil cationic protein (ECP), fibrinogen, interleukin (IL)-5 and IL-8. Sputum treated with DTT compared with PBS had lower proportions of viable cells (median 66 versus 74%; p=0.003). In contrast, DTT-treated sputum had higher total cell counts (median 8.8 vs 2.8 x 10(6) mL(-1); p<0.001) and levels of ECP (median 1340 vs 584 mg x L(-1); p<0.001) The measurements were similar with respect to the proportion of eosinophils, neutrophils, lymphocytes, macrophages, and fluid-phase fibrinogen, IL-5 and IL-8. We conclude that dithiothreitol disperses cells more effectively and that this might account for the higher levels of eosinophil cationic protein. Dithiothreitol may affect cell viability, but the changes are not relevant with respect to cell counts. Additionally, dithiothreitol does not seem to influence the other measurements performed.
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PMID:Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline. 919 39


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