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)

Two major issues severely limit the studies of human recombinant cytokines/growth factors in nonhuman primates. First, assays and reagents specific for the detection and quantitation of human cytokines do not all function when utilized to detect/quantitate the nonhuman primate cytokines. Second, although most of the human cytokines appear to induce similar, if not identical, biologic function when used with cells from nonhuman primates in vitro or in vivo, they invariably induce Ab responses in vivo, precluding their repeated and/or continued use in vivo. Our laboratory has thus initiated studies to clone, sequence, and prepare recombinant cytokines from nonhuman primates and to define assays and reagents for their detection and quantitation at the nucleic acid and protein level. The data that were derived from such studies show that the nonhuman primate cytokines IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 alpha, IL-12 beta, IL-15, IFN-alpha, IFN-gamma, and TNF-alpha share 93 to 99% homology at the nucleic acid and protein level with the human equivalents. The most prominent differences between human and nonhuman primate cytokine sequences were noted for IL-1 alpha/beta, IL-2, IL-8, IFN-alpha, IFN-gamma, and IL-12 beta. The aligned sequences of cytokines for human and several nonhuman primate species are provided herein, and a phylogenetic analysis of the published sequences of select cytokines from other species, along with those of the nonhuman primates, are described. In addition, comparative analysis of the relative bioactivity of our immunoaffinity-purified recombinant rhesus macaque IL-4, IL-15, and IFN-gamma with commercially available human recombinant cytokines is described herein.
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PMID:Comparative sequence analysis of cytokine genes from human and nonhuman primates. 756 Nov 2

Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in peripheral tissues, may also contribute to the powerful negative feedback actions of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present study we have used (1) an in vitro model to examine the influence of a specific neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of dexamethasone to suppress the cytokine-induced release of the 41-amino acid corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the rat hypothalamus and (2) a passive immunization protocol to assess the contribution of LC1 to the inhibitory actions of dexamethasone on the HPA responses to immunological (i.p. injection of interleukin 1 beta, IL-1 beta) and surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml), IL-6 (10 ng/ml) and IL-8 (1 ng/ml) each caused significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP from hypothalami removed from rats adrenalectomized 10-12 days before autopsy; these responses were readily inhibited by preincubation of the tissue with dexamethasone (10(-7) M). The inhibitory actions of the steroid were attenuated and, in many instances, abolished by inclusion in the medium of a monoclonal anti-LC1 antibody (LC1 mAb, diluted 1:15,000); an isotype-matched control antibody (antispectrin alpha+beta, diluted 1:15,000) was ineffective in this regard. IL-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated similar increases in the release of CRF-41 and AVP from hypothalami from intact rats which were effectively blocked by dexamethasone (10(-7) M). However, although the inhibitory actions of the steroid on the pharmacologically evoked release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000), the steroid blockade of AVP release was not. In vivo, rats pretreated with either a polyclonal anti-LC1 antibody (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of a nonimmune sheep serum (NSS) responded to immunological (IL-1 beta, 3 micrograms/kg i.p.) or surgical (laparotomy under ether anaesthesia) trauma with significant increases in the serum ACTH and corticosterone concentrations. In the NSS-treated groups, dexamethasone (100 micrograms/kg), which had no effect on the prestress concentrations of ACTH and corticosterone in the blood, completely prevented the HPA responses to both IL-1 beta and laparotomy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunoneutralization of lipocortin 1 reverses the acute inhibitory effects of dexamethasone on the hypothalamo-pituitary-adrenocortical responses to cytokines in the rat in vitro and in vivo. 756 34

Dendritic cells are the most potent antigen-presenting cells of the immune system. Although dendritic cells are likely to secrete selective cytokines that facilitate antigen presentation, the difficulty in isolating pure dendritic cells in sufficient numbers has made assessment of this function imprecise. In this study, pure populations of CD83+ human blood dendritic cells were isolated by previously established enrichment procedures and subsequent cell sorting. Cytokine gene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta, interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes, MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1-309 expression induced upon activation. Resting and activated CD83+ dendritic cells also expressed receptors for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect immunofluorescence staining. These results indicate that dendritic cells have the ability to produce a variety of soluble factors which are likely to contribute substantially to the potent allostimulatory activity of these cells.
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PMID:A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells. 757 30

Approximately 44% of patients develop osteoarthritis (OA) following rupture of the anterior cruciate ligament (ACL) if the injury is left unrepaired. Restoring knee stability through reconstruction, while providing symptomatic relief, has not been shown to reduce the incidence of degenerative changes. In fact, recent studies have shown that 50%-60% of ACL-reconstructed patients go on to develop degenerative changes or frank osteoarthritis. In light of these data, our group suggests that the cause of post-traumatic osteoarthritis is not biomechanical but biochemical. To test this hypothesis, we measured levels of nine cytokines which are important in modulating physiological and pathophysiological metabolism of cartilage in knee joint synovial fluid following ACL rupture. Our patient population contained both acute and chronic ACL ruptures. A total of 84 samples were collected and analyzed by enzyme-linked immunosorbent assay. On the basis of the data collected, we were able to identify subgroups of patients who, on the basis of their synovial fluid cytokine profile, may be at greater or lesser risk of developing post-traumatic OA. In general, patients displayed concentrations of interleukin-1 alpha (IL-1 alpha), basic fibroblastic growth factor (bFGF), transforming growth factor-beta (TGF-beta), granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-6, and IL-8 that we interpreted as being consistent with an inflammatory reaction. Of great interest is the fact that the levels of these cytokines were very similar in patients 4 weeks after injury and in chronic patients, leading us to hypothesize that a chronic smoldering inflammatory reaction persists after resolution of the acute effusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synovial fluid cytokine concentrations as possible prognostic indicators in the ACL-deficient knee. 758 75

A. The development of fetal Immune system 1. Complement: Alternative pathway is dominant in the development of fetal complement. 2. Neutrophil function: Phagocytosis in full term infants was increased to be adult-level, but bactericidal function was decreased. 3. NK activity: NK activity in full-term infants was significantly lower than in adults, however, IL-2-augmented NK activity did not indicate any significant difference with levels in adults. In pre-32 week infants both NK and IL-2-augmented NK activity were further decreased as opposed to in full-term infants. 4. LAK activity: LAK activity was fully developed already in 19 week infants, indicating that auto-monitoring of mutant cells is already under control from the early stages of fetal development. 5. Antibody production: Antibody production in infants was significantly decreased in comparison to adults. Reduced cytokine (IL-1, BCDF) production were considered to be the causal factors. 6. IL-2, IL-2R: In IL-2 production, no difference was recognized between normal neonates and adult subjects. In contrast, a significantly higher value of IL-2 production was observed for premature neonates born between 16 and 36 GW, compared with adults. IL-2 production and IL-2R system is fully developed at 22 weeks. 7. BCDF gamma, BCDF mu: Reduced compared to that of adults. 8. IL-6, IL-8, G-CSF: Much higher levels were found in cases of intrauterine infection, particularly in cases of premature delivery. The cytokine levels were 20-to-30-fold higher in chorioamnitis-positive premature delivery group. 9. M-CSF: M-CSF is increased, M-CSF may play a role in decidual function and placental function by the autocrine and paracrine system. 10. IL-1 alpha, IL-1 beta, IL-6: These production by macrophages was diminished in aborted fetuses, premature infants and IUGR infants. However, in the infants of mother with intrauterine infection, cytokine production was elevated to the level in full term infants and adults. 11. IFN gamma: Production of IFN gamma by memory T cells was diminished in premature infants. B. The vertical transmission of HTLV-I. The routes of vertical transmission of HTLV-I are intrauterine, intra-birth canal and via breast milk. Bottle-feeding is an effective way of avoiding mother-to-child infection. However breast milk is necessary for optimal infant nourishment, so we use -20 degrees C for 12 hours freeze-thawing of breast milk.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The viewpoints of viral vertical transmission from fetal neonatal immunologic aspects]. 759 81

An immunohistochemical technique was used to examine whether there was a colocalization of cytokine-specific receptors with cytokine-expressing cells. We have previously shown that there is extensive cytokine production and secretion in the rectal mucosa in shigellosis (interleukin 1 alpha [IL-1 alpha], IL-1 beta, IL-1ra, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha [TNF-alpha], TNF-beta, gamma interferon, granulocyte-macrophage colony-stimulating factor, and transforming growth factor beta [TGF-beta]) (R. Raqib, A. A. Lindberg, B. Wretlind, P. K. Bardhan, U. Andersson, and J. Andersson, Infect. Immun. 63:289-296, 1995; R. Raqib, B. Wretlind, J. Andersson, and A. A. Lindberg, J. Infect. Dis. 171:376-384, 1995). Kinetics for receptor expression was compared with that for cytokine synthesis in the inflamed rectal mucosa from Shigella-infected patients during acute (2 to 6 days after onset of diarrhea) and convalescent (30 to 40 days after onset) stages. Quantification of receptor expression was assessed by computer-assisted analysis of video microscopic images. A selective down-regulation of the receptors for gamma interferon, tumor necrosis factor (TNF receptor [TNFR] type I), IL-1 (IL-1 receptor [IL-1R] types I and type II), IL-3, IL-4, and TGF-beta (TGF-beta receptor type I) was observed at the onset of the disease, with a gradual reappearance during the convalescent stage. However, IL-2R, IL-6R, granulocyte-macrophage colony-stimulating factor receptor, TNFR type II, and TGF-beta receptor type II showed no change in expression during the study period and were comparable to controls. Cytokine receptors were predominantly located to the epithelial layer of the mucosal surface and crypts, with variable expression patterns in the lamina propria. A time-dependent kinetic curve was seen for the soluble IL-2R (sIL-2R), sIL-6R, and sTNFR types I and type II shed in stool at the acute stage similar to that observed for cytokine secretion in stool but at four- to six-times-lower concentration. In contrast, soluble receptor levels in plasma were 100-fold higher than the cytokine levels. The results suggest a dissociation in immune regulation between cytokine production and cytokine receptor expression. The down-regulation of the receptors in acute shigellosis was probably a consequence of cytokine-induced internalization and shedding of the receptors during signal transduction as well as due to programmed regulatory roles played by cytokines and the bacterial antigens.
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PMID:Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1 (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors at the local site during the acute phase of Shigella infection. 762 34

The effects of Porphyromonas gingivalis lipopolysaccharide (P-LPS) and Escherichia coli lipopolysaccharide (E-LPS) on the gene expression and production of inflammatory cytokines of human periodontal ligament fibroblasts (HPLF) were examined by a Northern (RNA blot) assay and enzyme-linked immunosorbent assay, respectively. mRNAs for interleukin-6 (IL-6), IL-8, and transforming growth factor beta (TGF-beta) were detected in HPLF cells, but IL-1 alpha, IL-1 beta, tumor necrosis factor alpha, transforming growth factor alpha, and granulocyte-macrophage colony-stimulating factor were not detected by reverse transcription-PCR. The expression of TGF-beta mRNA was not influenced by either LPS. P-LPS (1 to 10 micrograms/ml) and E-LPS (100 micrograms/ml) markedly stimulated the expression of IL-6 and IL-8 mRNAs compared with the control. The synthesis of IL-6 and IL-8 was also stimulated by 10 and 100 micrograms of both LPSs per ml, but IL-8 synthesis was not stimulated with E-LPS at 1 microgram/ml. Secretion of IL-6 and IL-8 into the culture medium was detected at 6 and 3 h, respectively, after exposure to P-LPS (10 micrograms/ml). These findings suggested that P. gingivalis leads to periodontal tissue destruction and alveolar bone resorption through IL-6 and IL-8 released from HPLF cells stimulated with its LPS.
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PMID:Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. 764 93

Fibrosis of the pulmonary parenchyma is a frequent and serious complication of scleroderma (systemic sclerosis, SSc), resulting in significant morbidity and mortality. During the past decade data have accumulated in support of an inflammatory process affecting the alveoli and distal airways that culminates in irreversible fibrosis in many SSc patients. Recent findings indicate the presence of lung fibroblasts with altered phenotype and biologic activity (myofibroblasts), perhaps arising from the influence of cytokines on resident lung fibroblasts. Acute-phase inflammatory cytokines such as IL-1 alpha, TNF-alpha, MIP-1 alpha, IL-8 and RANTES are increased in SSc bronchoalveolar lavage (BAL) fluid, as is thrombin, a potent mitogen for lung fibroblasts. Chronic-phase inflammatory and fibrogenic cytokines such as PDGF and TGF-beta are also present in increased amounts in SSc BAL fluid. The inciting event(s) and the process(es) leading to the perpetuation of fibrosis in SSc are unknown. Treatment of SSc lung disease has been empiric and generally disappointing, and it is likely that effective treatment awaits a better understanding of the biological events that regulate collagen and other extracellular matrix synthesis.
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PMID:Interstitial lung disease of systemic sclerosis. 765 Apr 24

Interleukin-1 alpha (IL-1 alpha) is a cytokine with a myriad of potent proinflammatory effects. Neutrophils are important immune effector cells in allergic and inflammatory lung diseases. We examined the effects of IL-1 alpha on human neutrophil migration across naked filters and human umbilical vein endothelial (HUVE) cell and type II-like pulmonary epithelial cell (A549) monolayers cultured on these filters. IL-1 alpha from 10(-13) to 10(-9) M induced dose-dependent neutrophil migration through both HUVE and A549 cellular monolayers but not through naked filters. Neutrophil migration was consistently greater through A549 monolayers compared with HUVE monolayers. IL-1 alpha-induced neutrophil migration was also time dependent, and the kinetics of neutrophil migration through HUVE and A549 monolayers were similar. Significant migration through either monolayer was not observed until 2 h, and maximal migration occurred at 3 h through A549 and 5 h though HUVE cellular monolayers. Supernatants of IL-1 alpha (10(-11) M)-stimulated HUVE and A549 monolayers induced significantly more migration of neutrophils across naked filters than 10(-11) M IL-1 alpha itself, suggesting the release of soluble secondary chemotactic factor(s). Pretreatment of HUVE and A549 monolayers with actinomycin D inhibited both IL-1 alpha-induced production of soluble chemotactic factor(s) and transcellular migration by > 90%. Supernatants from IL-1 alpha-treated HUVE and A549 cells contained significant concentrations of interleukin 8 (IL-8), and coincubation of these supernatants with anti-IL-8 inhibited approximately 50% of supernatant-induced chemotaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-8 mediates interleukin-1 alpha-induced neutrophil transcellular migration. 765 88

Infection with the protozoan parasite Entamoeba histolytica results in a high mortality worldwide. To initiate infection, E. histolytica trophozoites in the bowel lumen penetrate the epithelium, and cause extensive lysis of host cells. The acute amebic lesions in animal models are characterized by infiltration with inflammatory cells, particularly neutrophils. The acute host response is likely important for determining whether the infection will spread systemically, but little is known regarding the signals which initiate an acute inflammatory response to E. histolytica. In the studies reported herein, we used an in vitro model system to define the proinflammatory signals produced by epithelial and other host cells in response to infection with E. histolytica trophozoites. Coculture of human epithelial and stromal cells and cell lines with trophozoites is shown to increase expression and secretion of an array of chemoattractant and proinflammatory cytokines, including IL-8, GRO alpha, GM-CSF, IL-1 alpha, and IL-6. Moreover, high-level secretion of those cytokines is regulated by the paracrine action of cytolytically released IL-1 alpha. A second mechanism for trophozoite-induced IL-8 production involves trophozoite-target cell contact via a galactose-inhibitable amebic adherence protein, and appears to be mediated through increased intracellular calcium levels. These studies define novel mechanisms through which acute inflammation can be initiated in the host in response to a cytolytic pathogen, such as E. histolytica.
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PMID:Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha. 765 1


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