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)

Recent studies suggest that tumor necrosis factor (TNF) family members such as TNFalpha and lymphotoxin alphabeta (LTalpha1beta2) are important in the development of follicular dendritic cells (FDCs) and maintenance of FDC function. In this study we used FDC-like cells (FDC-LC) cultured from normal human tonsil and investigated the effects of TNF and LTalpha1beta2 on expression of adhesion molecules and the production of cytokines and chemokines. TNF and LTalpha1beta2 both increased the expression of VCAM-1 and ICAM-1 on FDC-LC. In addition, IL-4 with LTalpha1beta2 synergistically increased the expression of VCAM-1, but not ICAM-1. Cytokine IL-6 and IL-15 mRNAs were induced following stimulation with TNF and LTalpha1beta2. These two cytokines were present in FDC-LC supernatants by ELISA and increased following TNF and LTalpha1beta2 stimulation. We also examined FDC-LC for chemokines, which affect B cells, including IL-8, SDF-1, MIP3beta/ELC, and BCA-1/BLC. SDF-1 mRNA and protein were expressed by FDC-LC, and following stimulation with TNF and LTalpha1beta2, decreases in both were observed. Therefore, TNF and LTalpha1beta2, which are produced by activated B cells, increased the expression of adhesion molecules and cytokines from FDC-LC, potentially providing key signals to support germinal center B cell survival and differentiation.
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PMID:Functional effects of TNF and lymphotoxin alpha1beta2 on FDC-like cells. 1100 11

This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation. IL-8 at the higher concentrations tested (> or = 100 ng/ml) was unable to induce HIV-1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only marginally reduced. HIV-1 replication in acutely infected U937 cells was also significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1 cells by tumour necrosis factor-alpha (TNF-alpha) remained unaffected by the addition of IL-8. HIV-1 induction by IL-1beta, IL-6 and TNF-beta, cytokines grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not significantly alter the effect of IL-1beta, synergized with IL-6 in enhancing, and marginally suppressed TNF-beta-induced HIV-1 expression. IL-8 suppressed granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhanced interferon-gamma (IFN-gamma)-induced HIV-1 expression in a dose-dependent manner. Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its effect at the time of HIV-1 induction or at a postinduction stage. Furthermore, IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV-1 and IL-8. These results show that IL-8, typically a non-inducer, can differentially modulate HIV-1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL-8.
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PMID:Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines. 1101 65

Interleukin-18 (IL-18) is not only a co-stimulus for the induction of interferon-gamma but also has direct proinflammatory effects by inducing tumor necrosis factor-alpha (TNF-alpha), IL-1, IL-8 and IL-6. However, the cascade of events leading to induction of cytokines by IL-18 is unclear. The aim of the present study was to investigate whether murine IL-18 stimulates production of proinflammatory cytokines, and to assess whether induction of second-wave cytokines such as IL-6 by IL-18 is driven by intermediary induction of endogenous cytokines of the TNF family or IL-1beta. When mouse peritoneal macrophages were stimulated in vitro with recombinant murine IL-18, there was a dose-dependent induction of TNF, IL-1alpha, and IL-1beta. IL-6 synthesis was also strongly induced by IL-18 and, as revealed by studies in knockout mice, this production was not dependent on interactions between endogenous cytokines of the TNF/TNF receptor family: TNF-alpha, lymphotoxin-alpha, Fas/Fas ligand (L) or CD40/CD40L. Moreover, the induction of IL-6 was also independent of endogenous IL-1beta, as macrophages isolated from IL-1beta deficient mice produced normal amounts of IL-6 after stimulation with IL-18. In conclusion, murine IL-18 has pleiotropic proinflammatory activities by inducing production of TNF-alpha, IL-1alpha, IL-1beta and IL-6, which could have important consequences for the pathophysiology of infectious and autoimmune diseases.
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PMID:Interleukin-18 induces production of proinflammatory cytokines in mice: no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1beta. 1106 90

Spontaneous secretion of interleukin 8 (IL-8) was higher in latently infected U1 cells than in acutely infected or uninfected parental U937 cells. However, the induction of IL-8 by various cytokines (IL-1 alpha, TNF-alpha, IL-6, TNF-beta, GM-CSF, IFN-gamma) was significantly reduced in U1 cells. Cytokine modulation of IL-8 production in U937 cells acutely infected with a T cell-tropic strain (IIIB) or monocytotropic strain (ADA) of human immunodeficiency virus 1 (HIV-1) (HIV-1IIIB and HIV-1ADA) was variable and showed strain-specific differences. The obtained results showed that the in vitro induction of IL-8 is impaired in promonocytic cells latently infected with HIV-1 and is differently modulated under acute conditions of infection depending on the IL-8 inducing cytokine and on the infecting virus strain.
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PMID:Cytokine-induced interleukin-8 production is depressed in chronic as opposed to acute human immunodeficiency virus 1 infection of promonocytic cells. 1115 65

Designer drug etanercept (TNFR:Fc) is an inhibitor of TNF-alpha that binds with greater affinity than membrane receptors. Its full immunomodulatory effects are unknown. Approved for rheumatoid arthritis, its therapeutic potential in Crohn's disease has yet to be explored. We describe the course of a steroid-dependent patient with Crohn's disease given etanercept, and its effects on cytokine protein and mRNA expression and transcription factor activity in human leukocytes. Etanercept 25 mg s.c., was given twice weekly for 1 month. Weekly ESR, disease activity index, prednisone requirement, and serum cytokines were determined. In vitro, effects of physiologic concentrations of etanercept on cytokine protein and mRNA, and NFKB and GR transcription factor activity, were determined using MOT and U937 cell lines and peripheral blood mononuclear cells. Rapid clinical, biochemical, and immunologic improvement occurred, but obstruction due to stricture developed after 4 weeks. In vitro, constitutive and stimulated production of TNF-beta, IL-1beta, MIP-1beta, and IL-8 by normal mononuclear cells declined with etanercept, detectable TNF-alpha increased. MOT TNF-alpha expression tripled, mRNA for IL-12 p40 doubled, GR activity declined in U937 cells, NFKB was unaffected. Etanercept has complex immunomodulatory effects, and may be useful in Crohn's disease, but acutely decreased inflammation could worsen stricture.
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PMID:Immunomodulatory effects of etanercept (TNFR:Fc) and its use in a patient with Crohn's disease. 1145 80

L82, a novel anaplastic large cell lymphoma (ALCL) cell line was established from the pleural effusion of a 24-year-old patient with recurrent ALCL. L82 cells showed the typical morphologic features of ALCL cells with irregular, often indented, nuclear profiles, prominent nucleoli, and abundant cytoplasm. The immunoprofile of L82 corresponds to that seen typically in primary ALCL cells, with positivity for CD30, EMA, CD3, CD4, CD25, CD71, TIA1, and granzyme B; the cells were negative for EBV-related antigens. Cytogenetic analysis showed a complex, near triploid karyotype with 72-77 chromosomes, including the ALCL specific translocation t(2;5)(p23;q35). Chromosomal analysis revealed a number of secondary structural alterations including amplification of 7q21-31, 1q, and 6p, and gain of chromosomal material in 8q (affecting the c-myc gene). The rearrangement of the T-cell receptor-gamma locus shows that L82 is clonally derived from T-lineage lymphoid cells. mRNAs for interleukin 7 (IL-7), IL-8, IL-9, IL-10, TNF-beta, and for the IL-7 and IL-9 receptor were found. These data show that the T-helper cell (Th)1/Th2 balance was polarized to Th2. L82 were inoculated intraperitoneally into 4 week-old SCID mice and produced a disseminated tumor within 4-6 weeks. Morphological, immunohistochemical, and molecular genetic investigation confirmed that the xenograft and the original ALCL tumor were identical. SCID mice xenografted with the human ALCL cell line, L82, provide a useful model system for the investigation of the biology of ALCL and of new therapeutic approaches, such as specific immunotherapy.
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PMID:Characterization of a novel human anaplastic large cell lymphoma cell line tumorigenic in SCID mice. 1190 23

Although Fas (APO-1/CD95) is expressed ubiquitously and induces cell death, it is also known to mediate other responses such as inflammation and angiogenesis in vivo. Previously, we have reported that Fas ligation induces selective expression of chemokines (IL-8 and MCP-1) in human astroglioma cells in vitro. In this study, we investigated whether Fas ligation can induce expression of other cytokines. Expression of IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, IFN-beta, IFN-gamma, LT-beta, TGF-beta, TNF-a and TNF-beta mRNA levels in CRT-MG human astroglioma cells upon Fas ligation was investigated using RNase protection assay (RPA). We found that IL-6 mRNA is selectively induced upon Fas ligation, and IL-6 mRNA and protein expression was further investigated using single probe RPA and ELISA. To investigate the in vivo expression of IL-6, human brain specimens were homogenized and ELISA was performed for IL-6 expression. Herein, we demonstrate that: (1) Among these cytokines, only IL-6 was induced upon Fas ligation in a dose- and time-dependent manner; (2) A selective p38 MAP kinase inhibitor, SB202190, and a MEK inhibitor, U0126, suppressed induction of IL-6 mRNA and protein expression by Fas ligation; and (3) Glioblastoma multiforme samples (n = 11) contain significantly higher levels of IL-6 compared to those of control brains (n = 5), which correlate with increased levels of Fas. These results suggest that the Fas-FasL system may play a role in the regulation of tumor growth and survival by inducing the pleiotropic cytokine IL-6.
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PMID:Fas engagement increases expression of interleukin-6 in human glioma cells. 1194 22

The tumor necrosis factor alpha (TNF-alpha) -308 G/A and TNF-beta NcO1 polymorphisms have been described to be associated with an increased risk for sepsis in critically ill patients. Functional consequences associated with these polymorphisms remain unclear. We compared the genotype distribution of these TNF polymorphisms with susceptibility to severe sepsis and leukocyte function in blunt trauma patients (n = 70; mean injury severity score, 24 points [range, 4 to 57). Severe sepsis was defined according to the American College of Chest Physicians-Society of Critical Care Medicine consensus conference criteria. Genotyping for the NcO1 polymorphism (alleles TNFB1 and TNFB2) was performed by PCR and digestion of the products with NcO1, and that for the TNF-alpha -308 G/A polymorphism (alleles TNF1 and TNF2) was performed by real-time PCR. Leukocyte function was assessed by measurement of the production of endotoxin-induced cytokines (TNF-alpha, interleukin-6 [IL-6], and IL-8) in whole blood. TNF-alpha, IL-6, and IL-8 were determined by enzyme-linked immunosorbent assay. For the genotypes of the TNF-alpha -308 G/A polymorphism, differences in the frequency of development of severe sepsis were not detectable. Patients developing severe sepsis after trauma were significantly more likely to possess a homozygous genotype of the TNF-beta NcO1 polymorphism. Compared with heterozygotes, the odds ratio for the TNFB2/B2 genotype for the development of severe posttraumatic sepsis was 11 (P = 0.01), and that for the TNFB1/B1 genotype was 13 (P = 0.014). TNF-alpha -308:TNF-beta NcO1 haplotype analysis showed that the TNFB2:TNF2 haplotype is significantly negatively associated with development of severe sepsis. Patients homozygous for the TNFB1 or TNFB2 allele showed a persistently higher cytokine-producing capacity during at least 4 to 8 days after trauma than the heterozygotes. In patients homozygous for the TNF1 allele, a higher TNF-alpha- and IL-8-producing capacity was found only at day 1 after trauma. Although the TNF-beta NcO1 polymorphism appears to be less likely to be causative for development of severe sepsis after trauma, it is thus far the only genetic marker identified which can be used as a relevant risk estimate for severe sepsis in trauma patients immediately after the injury.
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PMID:Tumor necrosis factor gene polymorphisms, leukocyte function, and sepsis susceptibility in blunt trauma patients. 1241 51

Interleukin-8 (IL-8) has been identified as an angiogenesis factor (AF) as well as a tumor cell chemotactic factor and mitogen. Recent in vivo studies have demonstrated the expression of IL-8, IL-1 and TNF, as well their receptors, on various sub-populations of tumor cells in human breast cancer (HBC). Since pro-inflammatory cytokines such as IL-1 and TNF are known inducers of IL-8 in non-tumor cells, we hypothesize that IL-1/TNF may act as an IL-8 inducer in HBC, and thus enhance HBC tumor progression. To begin to test this hypothesis, we evaluated the ability of: a) human breast cancer cell lines (BCC) and normal human breast epithelial cell lines (BEC) to produce IL-8 in vitro; and b) IL-1 and TNF to regulate the expression of IL-8. In general, basal IL-8 expression was low in all 8 cell lines examined. TNF-alpha and TNF-beta induced a 3- to 24-fold increase in IL-8 protein expression of BEC, and a 2- to 8-fold increased IL-8 expression in estrogen-independent BCC cell lines and no significant IL-8 expression in estrogen-dependent cell lines. Conversely, IL-1alpha and IL-1beta, induced a 5- to 104-fold stimulation of BEC and a 330 to 1,138-fold increase in IL-8 expression in estrogen independent BCC. These observations demonstrate the ability of HBC cells to produce IL-8 in vitro and further indicate that IL-1 is a potent inducer of IL-8 expression by BEC and BCC. Furthermore, this in vitro data support the hypothesis, that within the HBC tumor microenvironment, tumor cells exist that respond to pro-inflammatory cytokine (IL-1) stimulation (i.e. MDA-MB-231) and those that do not (i.e. MCF-7). Additionally, HBC tumor cell lines that can be induced to express high levels of IL-8 tend to be associated with a more aggressive phenotype.
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PMID:In vitro demonstration of breast cancer tumor cell sub-populations based on interleukin-1/tumor necrosis factor induction of interleukin-8 expression. 1279 62

Cytokines play an important role in controlling the homoeostasis of the immune system. Infection with HIV results in dysregulation of the cytokine profile in vivo and in vitro. During the course of HIV-1 infection secretion of T-helper type 1 (Th1) cytokines, such as interleukin (IL)-2, and antiviral interferon (IFN)-gamma, is generally decreased, whereas production of T helper type 2 (Th2) cytokines, IL-4, IL-10, proinflammatory cytokines (IL-1, IL-6, IL-8) and tumour necrosis factor (TNF)-alpha, is increased. Such abnormal cytokine production contributes to the pathogenesis of the disease by impairing cell-mediated immunity. A number of cytokines have been shown to modulate in vitro HIV-1 infection and replication in both CD4 T lymphocytes and cells of macrophage lineage. HIV-inductive cytokines include: TNF-alpha, TNF-beta, IL-1 and IL-6, which stimulate HIV-1 replication in T cells and monocyte-derived macrophages (MDM), IL-2, IL-7 and IL-15, which upregulate HIV-1 in T cells, and macrophage-colony stimulating factor, which stimulates HIV-1 in MDM. HIV-suppressive cytokines include: IFN-alpha, IFN-beta and IL-16, which inhibit HIV-1 replication in T cells and MDM, and IL-10 and IL-13, which inhibit HIV-1 in MDM. Bifunctional cytokines such as IFN-gamma, IL-4 and granulocyte-macrophage colony-stimulating factor have been shown to have both inhibitory and stimulatory effects on HIV-1. The beta-chemokines, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES are important inhibitors of macrophage-tropic strains of HIV-1, whereas the alpha-chemokine stromal-derived factor-1 suppresses infection of T-tropic strains of HIV-1. This review outlines the interactions between cytokines and HIV-1, and presents clinical applications of cytokine therapy combined with highly active antiretroviral therapy or vaccines.
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PMID:Cytokines and HIV-1: interactions and clinical implications. 1295 22


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