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)

We have established nurse cell-like clones from long-term cultures of the human skin. These human skin nurse cell (HSNC)-like clones were type I collagen+, type IV collagen-, vimentin+, cytokeratin-, CD44+, CD54+, and weakly positive for VCAM-1, and easily identified by the pseudoemperipolesis that allowed T lymphocytes to migrate beneath the HSNCs. HSNCs and various T cell lines formed a typical complex in the hanging drop culture system. The majority of human and murine T cells, and some of the tumor cell lines other than T cells, including B lymphoma and myeloblastoma cells, migrated beneath the HSNC clones. HSNC clones produced various cytokines, including IL-6, IL-7, IL-8, IL-9, granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), macrophage CSF (CSF-1), TGF-beta 1, and c-kit ligand, but could not produce IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, TNF-alpha, or TNF-beta. These characteristics were similar to those of nurse cells established from the murine thymus. Furthermore, IFN-gamma-pretreated HSNC clones that expressed MHC class II Ags induced autologous mixed lymphocyte reaction (AMLR) in autologous PBMCs to proliferate and exhibit the cytotoxicity against altered autologous cells and various tumor cells. These results suggest that HSNCs play an important role in the immunoregulation at skin tissues.
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PMID:Establishment and characterization of nurse cell-like clones from human skin. Nurse cell-like clones can stimulate autologous mixed lymphocyte reaction. 808 78

Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand for lymphocyte function-associated antigen-1 (LFA-1), and thereby plays a crucial role in mediating cell-cell interactions in inflammatory reactions. Human eosinophils represent important effector cells in allergic skin diseases. To gain more insight into the capacity of eosinophils to physically interact with LFA-1-positive inflammatory leukocytes, in the present study ICAM-1 expression in eosinophils was investigated. Using fluorescence-activated cell sorter analysis, it could be shown that highly purified (> or = 95%) eosinophils from peripheral blood of non-atopic individuals do not constitutively express ICAM-1 molecules. However, stimulation of eosinophils with interferon gamma (IFN gamma), tumor-necrosis factor alpha (TNF alpha), or interleukin 3 (IL-3) markedly upregulated ICAM-1 surface expression in a time- and dose-dependent manner. Cytokine-induced ICAM-1 expression in human eosinophils was corroborated by Northern blot analysis. Accordingly, unstimulated eosinophils did not express significant amounts of ICAM-1 mRNA, but ICAM-1 mRNA expression could be markedly induced in these cells upon stimulation with IFN gamma plus TNF alpha. The combination of TNF alpha with either IFN gamma, IL-3, IL-5, or granulocyte/macrophage colony-stimulating factor (GM-CSF) increased ICAM-1 expression in a synergistic fashion, whereas IL-5 or GM-CSF by itself did not induce ICAM-1 expression. Cytokine-induced ICAM-1 expression was specific, because IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-7, IL-8, C5a, and platelet-activating factor did not significantly affect eosinophil ICAM-1 surface expression. In summary, these studies indicate that eosinophils may be activated to express the adhesion molecule ICAM-1 upon stimulation with selected inflammatory cytokines, which may allow adhesion-mediated cross-talk between eosinophils and LFA-1-positive cells. In addition, these data demonstrate for the first time a role for IL-3, IL-5, and GM-CSF in regulation of ICAM-1 expression in human cells.
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PMID:Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory cytokines. 809 60

The pathogenesis of cervical human papillomavirus (HPV) infection is influenced by the host's immune response. This response depends upon secretion of specific lymphokines to recruit and activate immune cells at the site of infection. To examine whether cervical cells enhance immune-responsiveness, secretion of lymphokines by cultures of normal cervical cells, HPV-immortalized cervical lines, and carcinoma lines was compared. Normal cervical cells constitutively secreted interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor. Lymphokines were also produced by exo- and endocervical epithelia in vivo. In contrast, four cervical cell lines immortalized by HPV DNAs and three carcinoma lines secreted selected lymphokines at significantly reduced levels. Interferon-gamma induced major histocompatibility class I and II proteins and intercellular adhesion molecule-I in normal cells, but results in immortal or carcinoma lines were variable. These results suggest that cervical epithelial cells have the potential to influence inflammation and immunity in the cervical mucosa. Furthermore, decreased expression of lymphokines and histocompatibility molecules by HPV-immortalized cervical cells suggests that similar alterations might accompany persistent HPV infections in vivo.
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PMID:Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines. 809 84

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

Induction of IL-8 gene expression was investigated in IL-2-stimulated circulating peripheral blood polymorphonuclear neutrophils (PMN). Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of IL-8. The IL-8 mRNA was first detectable by 3 h, followed by a continuous maintenance of high mRNA levels up to 18 h. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil-activating factors such as granulocyte macrophage-CSF and Candida albicans. The protein synthesis inhibitor, cycloheximide, had no detectable effect on levels of IL-8 mRNA expression in PMN incubated in medium alone; however, cycloheximide could selectively modulate IL-8 mRNA transcription in PMN, depending on the cytokine used. Cycloheximide did not affect or alter IL-8 mRNA induction in IL-2-treated PMN but abrogated it in granulocyte macrophage-CSF-treated PMN and super-induced the level of IL-8 mRNA in C. albicans-treated PMN. Of significance was the observation that IL-2 has no direct chemotactic effect on PMN, whereas the cell-free supernatants from IL-2-stimulated PMN show potent chemotaxis for freshly isolated PMN, which can be specifically blocked by anti-IL-8 Abs. These findings suggested that the induction of IL-8 gene expression in PMN by IL-2 may be involved in the recruitment of PMN into tissues during local IL-2 therapy in human cancer and in part contribute to tumor rejection.
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PMID:Induction of IL-8 gene expression in human polymorphonuclear neutrophils by recombinant IL-2. 814 38

The influence of pooled human IgG preparations for intravenous use (IVIg) on cytokine production induced by streptococcal pyrogenic exotoxin-A (SPE-A) was studied at the single-cell level using cytokine-specific monoclonal antibodies and indirect immunofluorescence or immunohistochemical staining. Mononuclear cells from healthy adult blood donors were stimulated with SPE-A alone or in the presence of IVIg. IVIg was added either prior to stimulation or 24 h after initiation of cultures, in an attempt to evaluate whether IVIg treatment could influence an already established systemic streptococcal disease. Cells were harvested after 48 or 72 h of culture and stained for the following cytokines: interleukin(IL)-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-2, tumor necrosis factor interferon(IFN)-gamma and TNF-alpha and TNF-beta and granulocyte macrophage-colony-stimulating factor. Stimulation with SPE-A lead to extensive lymphokine and monokine production. With the addition of IVIg prior to stimulation there was a strong reduction of blast transformation and an almost complete inhibition of lymphokine production, in particular in the synthesis of IFN-gamma and TNF-beta while the synthesis of IL-1 and IL-8 was either unaffected or increased. Adding IVIg 24 h after SPE-A stimulation also resulted in reduced blast transformation and decreased synthesis of IFN-gamma and TNF-beta. These results indicate an immunomodulatory potential by IVIg on streptococcally induced T cell activation and lymphokine production.
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PMID:Lymphokine production induced by streptococcal pyrogenic exotoxin-A is selectively down-regulated by pooled human IgG. 814 62

The present study investigates the effect of transforming growth factor (TGF)-beta on the production of IL-4 and IFN-gamma by the leukemia Th0 type cell line HUT78, by freshly isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-gamma, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-beta 1. TGF-beta 1 also reduced the accumulation of IL-4 and IFN-gamma specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-gamma production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-alpha or granulocyte macrophage colony stimulating factor had no effect. Because IL-2 is an important helper cytokine for the production of IL-4 and IFN-gamma, we investigated whether signal transduction through the IL-2 receptor is impaired by TGF-beta 1. We found that tyrosine phosphorylation in response to IL-2 in HUT78 cells was strongly inhibited by a short preincubation with TGF-beta 1. Evidence for an antagonistic role for TGF-beta 1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-beta 1 mediated inhibition of IL-4 and IFN-gamma production. Similar to its effect on HUT78 cells, TGF-beta 1 also inhibited IL-4 and IFN-gamma production by freshly isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-gamma are both negatively controlled by TGF-beta under conditions where IL-2 production is unaffected by a mechanism which partially involves an inhibition of IL-2/IL-2R signal transduction. These data identify TGF-beta and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-gamma production.
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PMID:Transforming growth factor-beta inhibits IL-4 and IFN-gamma production by stimulated human T cells. 818 98

Changes in cytosolic free Ca2+ influence important granulocyte functions like chemotactic behavior, adherence to endothelia, and phagocytosis. In the following study we used a simple reproducible procedure involving flow cytometry in combination with the fluorescent dye Fluo-3 to measure Ca2+ changes in human granulocytes. The aim of our study was to investigate the involvement of protein kinase C in regulating cytosolic free Ca2+ concentrations after stimulation of cells with IL-8 and fMLP. Both reagents induced a 5-6 fold increase in cytosolic Ca2+. Experiments conducted in Ca(2+)-free media showed a minor 18-29% decrease in cytosolic Ca2+ response, suggesting that intracellular Ca(2+)-stores are the main source for Ca2+ release after fMLP or IL-8 stimulation. Activators of protein kinase C, phorbol myristate acetate (PMA) and 1-oleyl-2-acetyl-sn-glycerol (OAG), inhibited cytosolic Ca(2+)-increase completely when induced by IL-8 and by 68-82% in the case of fMLP. Staurosporine, an inhibitor of protein kinase C, was able to attenuate or even abolish the PMA/OAG-effect. Our results show that changes in cytosolic Ca2+ due to IL-8 and fMLP signalling can be regulated by protein kinase C in human granulocytes. This regulatory role of protein kinase C involves some form of receptor modulation (i.e. phosphorylation, internalization, shedding).
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PMID:Protein kinase C regulates IL-8 and fMLP induced cytoplasmic Ca2+ increase in human granulocytes by receptor modulation measurements by flow cytometry. 826 89

Polymorphonuclear neutrophils (PMN) have long been thought to be short-lived, terminally differentiated cells incapable of synthesizing significant levels of protein, with their primary function being phagocytosis and the release of cytotoxic compounds. More recently, it has been demonstrated that PMN can produce a number of functionally diverse substances, including IL-1, IL-6, and IL-8. Although PMN express class I MHC Ag, it has not been definitely demonstrated that they can synthesize and express class II Ag. This would suggest that, although PMN can indirectly assist in the induction of an immune response through production of cytokines, they are incapable of acting as APC for CD4+ Th cells. We show that, in the presence of a defined medium (AIM V), human serum, and granulocyte-CSF, nearly 100% of isolated PMN can survive for up to 2 days in vitro. We also show that PMN express MHC class II when present as bystander cells in a monocyte/T cell Ag presentation assay for 44 h. In addition, granulocyte/macrophage CSF (GM-CSF), IFN-gamma, and IL-3 can induce class II on pure cultures of PMN, with GM-CSF appearing to be the most potent of the three cytokines. Furthermore, induction of class II on PMN is distinctly donor dependent, with PMN from some donors repeatedly showing very high, and others very low, induction of class II when treated with GM-CSF. Their potential to express class II suggests that PMN could play a significant role in immunoregulation and disease pathogenesis. The variation in class II induction on PMN from individual donors might explain previous failures to detect class II induction on PMN and could be a factor in the varied susceptibility of different individuals to autoimmune and inflammatory disorders such as the production of antibodies to PMN cytoplasmic components.
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PMID:Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. 833 42

Triakontatetraneuropeptide (TTN) is the major processing product of the endogenous anxiogenic peptide ligand of the benzodiazepine receptor, diazepam binding inhibitor. In the present study, we demonstrated by Northern blot analysis that the mRNA levels for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, granulocyte/macrophage colony-stimulating factor, IL-6, and IL-8 were significantly increased after 4 hr of incubation of human monocytes with lipopolysaccharide (LPS) and TTN (10(-11) M), compared with cells incubated with LPS alone. Exposure of monocytes for 20 hr to LPS and TTN (10(-11) M) also stimulated TNF-alpha, IL-1 beta and granulocyte/macrophage colony-stimulating factor release by 80%, 110%, and 98%, respectively, relative to the response elicited by LPS alone. Smaller stimulatory effects were observed using the prototypic pharmacological peripheral benzodiazepine Ro5-4864 (10(-11) M) (55%, 72%, and 62%, assessed by means of specific enzyme immunoassays). In contrast, TTN and Ro5-4864 did not modulate LPS-induced IL-6 and IL-8 production. Treatment with the cyclooxygenase inhibitor indomethacin increased IL-1 beta and TNF-alpha secretion but not that of IL-6 or IL-8. The observed stimulatory effects of TTN and indomethacin were not additive. Taken together, these findings suggest a common mechanism of action for TTN and indomethacin, involving PG formation. In this respect, TTN inhibited prostaglandin (PG) E2 production by 30%. The fact that the observed modulatory effects correlated with PG levels suggests the existence of a second-messenger pathway associated with the peripheral-type benzodiazepine receptor. These results indicate that human TTN differentially modulates the LPS-induced expression of proinflammatory cytokines, and they further support the concept that this endogenous psychoactive peptide could be involved in physiological control of the inflammatory response.
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PMID:Modulation of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide: evidence for a role of prostaglandins. 838 Aug 85


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