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 investigated, in five cell strains per experiment, whether several cytokines known or believed to have effects on bone resorption were produced by nearly homogeneous strains of cultured normal human osteoblast-like (hOB) cells that display virtually the complete phenotype of the mature osteoblast. In unstimulated hOB cells, we detected constitutive production of interleukin-6 (IL-6) (mean +/- SE, 122 +/- 32 pg/ml) and IL-8 (135 +/- 39 pg/ml), but not of IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF alpha). IL-1 beta in doses from 1-100 U/ml stimulated dose-dependent increases in IL-6 (r = 0.87; P less than 0.001) and IL-8 (r = 0.95; P less than 0.001). Similar increases occurred after stimulation with TNF alpha in doses from 3-300 U/ml. IL-1 beta and TNF alpha also stimulated GM-CSF production, but only at higher doses. 17 beta-Estradiol (10(-8) M) had no significant effect on the secretion of any of these cytokines, either constitutively or after stimulation with IL-1 beta or TNF alpha. Stimulated production of IL-4 was not detected after treatment with IL-1 beta or TNF alpha, and that of TNF alpha was not detected after treatment with IL-1 beta. We conclude that IL-6, IL-8, and GM-CSF, but not IL-4 and TNF alpha, are produced by highly differentiated normal human cells of the osteoblast lineage, but their secretion is not regulated by estrogen. However, we cannot exclude the possibility that estrogen regulation of these cytokines may occur during early stages of osteoblast differentiation.
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PMID:Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol. 157 80

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

Skin blisters induced by suction on the forearm of normal volunteers provide a convenient model to study the inflammatory response in vivo in man. In our study, after removal of the roof of the blister, i.e., the epidermis, the exposed floor of the blister (dermal-epidermal interface) was bathed with 70% autologous serum using a multiwell skin chamber. Migration of leukocytes (90-95% neutrophils) into the chamber fluid was detectable within 3 h, and appeared to plateau at 16-24 h. Sampling of the dermal-epidermal interface revealed primarily mononuclear cells during the first 8 h of the inflammatory response; however, their prevalence at 24 h was greatly diminished due to neutrophil infiltration. Accompanying the cellular immune response was the accumulation of inflammatory mediators in the bathing medium. The accumulation of IFN-gamma reached a plateau within 3 h; significant accumulations of the complement fragment, C5a, and of leukotriene B4 were also detected at 3 h. The accumulation of C5a did not peak until 5 h, whereas leukotriene B4 continued to accumulate through 24 h. IL-6 and IL-8 concentrations were minimal at 3-8 h but dramatic by 24 h while IL-1 beta, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were undetectable within 3-8 h, but markedly elevated by 24 h. There was little accumulation of IL-4 and no accumulation of IL-1 alpha or IL-2 during the 24-h period. The sequential appearance of mediators at an inflammatory focus suggests that a carefully regulated dynamic system is responsible for controlling the evolution of the inflammatory response.
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PMID:Dynamics of the cellular and humoral components of the inflammatory response elicited in skin blisters in humans. 160 84

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

We investigated the response of purified and cloned human thymic epithelial cells (TEC) to IL-1, IL-4, and IFN-gamma stimulation in vitro. IL-1 alpha strongly up-regulated the production of granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), IL-6, and IL-8, as measured by specific immunoenzymetric assays and by increased steady state mRNA levels. IL-4 or IFN-gamma did not induce these cytokines in TEC but in a sustained and dose-dependent manner down-regulated the IL-1-induced GM-CSF protein and mRNA levels. Only IFN-gamma, and not IL-4, suppressed the IL-1-induced G-CSF and IL-8 production, as shown at both the protein and mRNA levels. The inhibition was dose dependent, sustained for at least 96 h, and more pronounced for G-CSF than for IL-8. In contrast, both IL-4 and IFN-gamma enhanced the IL-1-induced IL-6 production. IL-4 and IFN-gamma had additive effects to increase IL-6 secretion and to more completely suppress the IL-1-induced GM-CSF. Analyses of cell surface molecules showed that intercellular adhesion molecule 1 (ICAM-1) expression on TEC was increased by IL-1 or IFN-gamma. IL-4 slightly down-regulated constitutive ICAM-1 levels but did not significantly modify the levels of expression induced by either IL-1 or IFN-gamma. MHC class II expression was induced by IFN-gamma but not by IL-1 or IL-4. The combination of IL-1 and IL-4 with IFN-gamma did not alter the levels of class II MHC Ag induced by IFN-gamma. In conclusion, TEC cytokine production and cell surface molecule expression are differentially regulated via a complex cytokine network. Our data suggest that developing T cells provide, in part, the signals controlling the function of their supporting stroma.
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PMID:IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells. 171 90

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
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PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.
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PMID:Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. 194 Jul 99

Hyper-IgE syndrome is a rare immunodeficient disorder characterized by recurrent severe staphylococcal infections of the skin and sinopulmonary tract, chronic eczematoid rashes, coarse facial features, mild eosinophilia, and markedly elevated serum IgE levels. Hyperimmunoglobulinemia D, depressed DTH, and varying degrees of pathogenesis of this syndrome is unknown. The clinical manifestations and the recent research findings indicated the followings: 1) increased production of IL-4: hyperimmunoglobulinemia E, increased number of Fc epsilon R(+)-cells in peripheral blood, 2) defective production of IFN-gamma: abnormal local inflammatory responses (formation of cold abscesses), chemotactic defect in the circulating neutrophils (abnormalities in IFN-gamma/IL-8 pathway), depressed DTH, 3) T-cell immunodeficiency?-chronic dermatitis? 4) genetic factors (frequent familial occurrence, characteristic facial appearance with broad nasal bridge). These observations led us to postulate that both the increased production of IL-4 and the defective production of IFN-gamma may be the immunopathological bases of this syndrome. Recently, these cytokines were demonstrated to be secreted by different subsets of helper T-cells, designated TH1 and TH2, in murine system, suggesting that the regulatory imbalances between IL-4 and IFN-gamma in this syndrome might be due to the differential activation or inactivation of these helper T-cell subsets.
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PMID:[Hyper IgE syndrome--a disease of imbalanced activation of helper T-cell subsets?]. 214 8

Peripheral blood monocytes are important mediators of inflammation via the generation of various bioactive substances, including the recently isolated and cloned chemotactic peptide IL-8. Through cytokine networking, monocyte-derived cytokines are capable of inducing IL-8 expression from non-immune cells. IL-4, a B and T lymphocyte stimulatory factor, has recently been shown to inhibit monocyte/macrophage function, including the ability to suppress monocyte-generated cytokines. We describe the in vitro inhibition of IL-8 gene expression and synthesis from LPS, TNF, and IL-1 stimulated peripheral blood monocytes by IL-4. IL-4 suppressed IL-8 production from stimulated monocytes in a dose-dependent fashion, with partial suppression observed at IL-4 concentrations as low as 10 pg/ml. The IL-4-induced suppressive effects were observed even when IL-4 was administered 2 h post-LPS-stimulation. The IL-4-induced inhibition of IL-8 mRNA expression was dependent on protein synthesis, as the suppressive effects of IL-4 were significantly negated by the addition of cycloheximide. Our findings suggest that IL-4 may be an important endogenous regulator of inflammatory cell recruitment, and adds further support to the potential role of IL-4 as a down-regulator of monocyte immune function.
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PMID:IL-4 inhibits the expression of IL-8 from stimulated human monocytes. 220 Aug 23

The role(s) of novel chemotactic cytokines as mediators in the pathogenesis of many acute and chronic disease states is becoming increasingly apparent. One of these cytokines, interleukin 8, is a product of both immune and non-immune cells. In this manuscript, we describe the suppression of IL-8 gene expression from stimulated monocytes by IL-4, while IL-4 had no suppressive effects on IL-8 gene expression from stimulated fibroblasts and endothelial cells. Our data suggest that IL-4 may function as an endogenous regulator of monocyte cytokine expression, including the chemotactic cytokine IL-8.
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PMID:Disparate regulation of interleukin 8 gene expression from blood monocytes, endothelial cells, and fibroblasts by interleukin 4. 220 28


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