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)

Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8), and interleukin-6 (IL-6) are pivotal in the regulation of hematopoiesis and immune responses. In mesenchymal cells, their expression is induced by tumor necrosis factor alpha (TNF) and other agents. We now show that, while induction of cytokine expression by TNF in human lung fibroblasts was parallel, glucocorticoid hormones differentially affected their production. Dexamethasone (1 mumol/L) concordantly repressed expression of GM-CSF, NAP-1/IL-8 and IL-6. RNA and protein levels were reduced to approximately 5%, 20%, and 30% of control cells, respectively, as determined by Northern blot analyses and immunoassays. A 50% reduction of RNA levels for all three cytokines occurred in the range of 1 hour. In contrast, dexamethasone (1 mumol/L) did not decrease M-CSF RNA levels and protein release. M-CSF RNA and protein levels were maintained even when dexamethasone (1 mumol/L) was present for the whole duration of a 48-hour TNF stimulation. Further experiments showed that dexamethasone downregulates expression of GM-CSF, NAP-1/IL-8, and IL-6 mainly by decreasing the mRNA stability of these cytokines, and that the dexamethasone-mediated repression of cytokine expression depends on ongoing protein and RNA syntheses. Our study suggests that glucocorticoid hormones repress expression of a set of cytokine genes important in conditions of stress. However, they seem not to affect M-CSF expression, which is likely to be more crucial in maintaining long-term functions of myeloid cells.
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PMID:Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. 137 Feb 8

The present study was designed to investigate the capacity of human mononuclear phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein (MCP), alternative acronyms JE, monocyte chemotactic and activating factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified monocytes were able to express high levels of MCP transcripts. In an effort to exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1, TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage-CSF, as well as inactivated streptococci, also induced MCP gene expression. Actinomycin D experiments indicated that induction of MCP in monocytes was gene transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy) blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In contrast, expression of the structurally related chemotactic cytokine IL-8 was superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma cells, indicating different mechanisms of regulation in mononuclear phagocytes vs cells of other lineages. The capacity of cells of the monocyte-macrophage lineage to produce a cytokine that recruits and activates circulating monocytes may be of considerable importance in inflammatory and immunologic reactions. Thus, the mononuclear phagocyte system can autonomously regulate the extravasation and activation of immature elements of the same lineage, a key event in inflammation and immunity.
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PMID:Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. 137 May 16

We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.
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PMID:In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions. 138 98

Astrocyte-enriched populations were established from human embryonic brain analyzed for their ability to synthesize cytokines potentially relevant for mechanisms of inflammation and immunity in the brain. Unstimulated astrocytes did not secrete significant IL-6, IL-8, macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), or granulocyte-CSF (G-CSF), as determined by specific ELISA and/or bioassay. With the exception of M-CSF mRNA, transcripts for the above factors were not detected in unstimulated astrocytes. On exposure of human astrocytes to IL-1 beta, high levels of IL-6, IL-8, M-CSF, G-CSF, and GM-CSF mRNAs were detected; moreover, active secretion of all the above cytokines was demonstrated. TNF-alpha was also able to stimulate IL-6, IL-8, M-CSF, GM-CSF, and G-CSF synthesis and secretion, but was generally less potent than IL-1 beta. No IL-3 mRNA or protein was detected in unstimulated or cytokine-treated astrocytes. IL-1 alpha and IL-1 beta mRNAs and proteins were not detected in unstimulated astrocytes, but were present in very small amounts after stimulation with TNF-alpha/IL-1 beta. No IL-6, M-CSF, GM-CSF, G-CSF, or IL-8 were induced by IL-1 beta or TNF-alpha in early primary cultures, which mainly contain undifferentiated neuronal/glial progenitor cells. These studies demonstrate for the first time the production of multiple cytokines by normal human astrocytes stimulated in culture by IL-1 beta and TNF-alpha. The capacity of human astrocytes to synthesize and release cytokines active on hemolymphopoietic cells supports the concept that these cells play an important role in the regulation of inflammatory and immune responses in a variety of brain pathologies.
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PMID:Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. 138 99

Human rIL-7 was studied for its effects on myeloid and erythroid progenitors from human bone marrow cells. IL-7 did not support the granulocytic/monocytic or erythroid lineage but exclusively stimulated eosinophil colony formation (CFU-Eo) (4 +/- 3 vs 48 +/- 17 CFU-Eo/10(5) nonadherent fraction-non-T cell (NAF-NT) cells). This supportive effect was not mediated by T cells or monocytes because similar results were obtained with or without T cell or adherent depleted cell fractions. In addition, it was shown that CD34+ sorted cells could be stimulated by IL-7 (0 vs 15 +/- 9 CFU-Eo/3 x 10(3) CD34+ cells) Furthermore studies with IL-3 or granulocyte-macrophage CSF (GM-CSF) demonstrated an additive effect on the IL-7 supported colony formation. Finally, experiments were performed with anti-IL-3, anti-GM-CSF, anti-IL-1, and anti-IL-5 to exclude the possibility that IL-7 indirectly stimulated the eosinophil progenitor cell. Anti-GM-CSF, anti-IL-1, or anti-IL-3 did not influence the supportive effects of IL-7. However, anti-IL-5 did abolish the effects of IL-7 on the eosinophil colony formation (69 +/- 15 vs 3 +/- 2 CFU-Eo/10(5) NAF-NT, n = 3). Similar results were obtained with CD34+ sorted cells. Moreover, IL-5 mRNA expression could be demonstrated in IL-7-stimulated NAF-NT cells. These data suggest that the supportive effects of IL-7 on eosinophil precursors are mediated by the endogenous release of IL-5.
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PMID:The supportive effects of IL-7 on eosinophil progenitors from human bone marrow cells can be blocked by anti-IL-5. 138 35

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5). We have investigated the modulatory role of IL-5 on N-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophil-activating factor (NAF/IL-8), platelet factor 4 (PF4), and cytokine-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a small chemotactic response toward PF4 but not to NAF/IL-8 and FMLP. Preincubation of eosinophils with low concentrations of IL-5 caused significantly increased responses toward PF4 and induced a significant chemotactic response toward FMLP and NAF/IL-8. In marked contrast, IL-5 (or IL-3) priming of eosinophils from normal donors resulted in a strong inhibition of GM-CSF-induced chemotaxis. A similar decrease in the chemotactic response toward GM-CSF was observed in eosinophils derived from allergic asthmatic individuals. This finding suggests that the latter eosinophils may have had a prior exposure to IL-5 (or IL-3). Washing of the cells after priming did not abrogate the inhibition of the GM-CSF response. Our data indicate that at low concentrations IL-5 is an important modulator of eosinophil chemotaxis, causing selective upregulation or downregulation of chemotactic responses toward different agents.
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PMID:Modulation of eosinophil chemotaxis by interleukin-5. 144 9

To study regulatory mechanisms influencing the synthesis and release of ET-1, a potent bronchoconstrictor, epithelial cells from guinea pig tracheas were cultured to test various cytokines for the synthesis of ET-1 and its precursor, big ET-1. Cytokines tested were divided into 4 groups, based on their potential modes of action. IL-8, TNF alpha and TGF beta transiently increased the synthesis of ET-1, while EGF, PDGF and GM/CSF promoted proliferation of ET-1 synthesizing cells. IL-1 enhanced the synthesis of ET-1 precursor without mitogenesis, whereas IL-2, IL-6 and IGF-1 induced both the synthesis of big ET-1 and mitogenesis. These observations suggest that cytokines involved in damage, inflammation and repair of the airway epithelial layer regulate the synthesis and release of ET-1 by multiple mechanisms, thereby influencing airway muscle tone.
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PMID:Regulation of endothelin-1 synthesis in cultured guinea pig airway epithelial cells by various cytokines. 151 Jun 83

Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.
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PMID:Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. 162 1

Both keratin synthesis and the formation of the horny layer are "classical" functions of human epidermal keratinocytes. In recent year a couple of interesting immunological functions of keratinocytes have been discovered. In the present review phagocytosis, production and secretion of cytokines (IL-1, IL-3, IL-6, IL-8, CSF, ECDF, IFN) and their ligands as well as the expression of selected cell surface receptors (HLA-DR, ICAM-1, Fc-gamma receptor) ligands are described.
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PMID:[The keratinocyte--a biologically active cell]. 169 21

The phospholipid platelet-activating factor (PAF) is a potent cell-derived bioactive molecule thought to be involved in diverse inflammatory processes. It has been shown that PAF can activate different leukocyte types and platelets, particularly in synergy with other agonists. In this study we examined the effect of PAF upon the release of histamine and leukotriene (LT) C4 by basophils when added alone and in combination with different agonists and cytokines. PAF by itself did neither induce histamine release nor the generation of LTC4 by basophils. However, basophils primed by the hematopoietic growth factors (hGF) IL-3, granulocyte-macrophage (GM)-CSF, or IL-5 (10 ng/ml) released preformed and de novo synthesized mediators in response to PAF at 10 to 100 nM concentrations. The extent of mediator release by hGF primed basophils in response to PAF was similar to that induced by an optimal concentration of monoclonal anti-IgE. Thus, similar to NAP-1/IL-8 and C3a, PAF efficiently stimulates mediator release in hGF-primed basophils only. However, PAF was clearly a more potent trigger of LTC4 formation in IL-3-primed cells than NAP-1/IL-8 or C3a. When PAF was used as a second trigger, the priming effect of IL-5 was less than that of IL-3 or GM-CSF, whereas the response for other IgE-independent agonists (i.e., C5a or FMLP) was augmented equally by all three hGF. IL-1 beta-pretreated basophils released minimal amounts of histamine in response to PAF. Neither TNF-alpha nor PAF, nor the combination thereof, was able to induce basophil mediator release. The efficiency of the different cytokines to prime for PAF responsiveness was strikingly similar to their capacity to enhance anti-IgE-induced mediator release. Similar to other IgE-independent agonists, the kinetic of mediator release in response to PAF was very rapid. PAF pretreatment of basophils did not enhance mediator release in response to diverse agonists, such as C5a and FMLP, in contrast to the capacity of PAF to augment the response of other leukocyte types to appropriate stimuli. Thus, depending on the presence of IL-3, GM-CSF, or IL-5, PAF is a potent basophil agonist capable of inducing histamine release as well as de novo synthesis of LTC4.
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PMID:Platelet-activating factor induces mediator release by human basophils primed with IL-3, granulocyte-macrophage colony-stimulating factor, or IL-5. 171 Oct 77


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