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)

The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.
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PMID:GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha. 800 13

Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Several of these cytokines can influence the growth of tumour cells as well as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous injection of 1 x 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6. 804 88

The mechanisms by which neutrophils migrate through the alveolar interstitium during acute lung inflammation are unknown. We wished to determine whether platelet-activating factor (PAF) and IL-8, two important mediators in neutrophil transendothelial migration, stimulated neutrophil adherence and motility on lung fibroblasts. Canine fibroblasts grown from lung explants were characterized by light and electron microscopy, and flow cytometry. Unstimulated neutrophils adhered poorly (less than 2%) to cultured fibroblasts. However, neutrophils stimulated with PAF (20-200 nM) showed a dose-dependent increase in adherence that was largely (70%) mediated by the beta 2 (CD11/CD18) integrins; adherence was less dependent (50%) on fibroblast intercellular adhesion molecule-1. Conversely, neutrophils stimulated with canine rIL-8 did not increase their adherence to fibroblasts. PAF-stimulated neutrophils were nonmotile on the surface of the fibroblast, but subsequent addition of rIL-8 (10(-8) M) induced motility that was entirely CD1 8 dependent. Fibroblasts stimulated with human rTNF-alpha or Escherichia coli endotoxin (LPS) were a significant source of IL-8 mRNA. In response to rTNF-alpha (50 U/ml), IL-8 mRNA was detected at 2 h by northern blot analysis; it peaked at 6 h and returned to baseline by 24 h. Fibroblasts stimulated with rTNF-alpha secreted IL-8 protein into the culture medium; secreted IL-8 was chemotactic for neutrophils. These data suggest that fibroblasts can function not only as an adhesive substrate, but also as a source of stimulation for neutrophil migration through the inflamed alveolar interstitium.
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PMID:Chemotactic factors stimulate CD18-dependent canine neutrophil adherence and motility on lung fibroblasts. 861 65

We previously showed that endothelial cells (EC) from the vasculature of human solid tumors have a decreased expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 as compared with normal tissue EC. This effect is explained by EC exposure to angiogenic factors. It is known that upregulation of endothelial adhesion molecules (EAM) is a sign of EC activation in inflammatory responses. We therefore tested the effect of angiogenic factors on upregulation of EAM on tumor EC and human umbilical vein EC (HUVEC) by proinflammatory cytokines. Incubation of tumor-derived EC in tumor necrosis factor alpha (TNF alpha) did result in expression levels of only 20% of the level of similarly treated normal tissue-derived EC. Pretreatment of HUVEC with 10 ng/ml basic fibroblast growth factor (bFGF) for 3 days, before TNF alpha- or interleukin-1 alpha (IL-1 alpha) stimulation, resulted in ICAM-1 levels of only 30% to 60% of cells without pretreatment. Also, the induction of vascular EC adhesion molecule-1 (VCAM-1) and E-selectin by TNF alpha was significantly inhibited by prior exposure to bFGF. Vascular endothelial growth factor had similar but less prominent effects. The effect of transforming growth factor-beta and IL-8 was studied as well. The functional relevance of the finding of a decreased EC inflammatory response was confirmed by adhesion assays. Our results show that tumor angiogenesis induces EC anergy. This may serve as a tumor-protecting mechanism by impairing the development of an efficient leukocyte infiltrate in tumors.
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PMID:Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. 869 14

Ischemia is an interruption of oxygen and nutrient supply to a determined area of tissue for a period of time. Because of the heterogeneity of various tissues with regard to their microvascular flow reserve and oxidative capacity, as well as their markedly different metabolic needs, a single critical Po2 level below which ischemia occurs is unlikely. This is why there are variations of tolerance to hypoxia within and among organs. In general, when Pao2 reaches approximately 5 torr there is already evidence, in some organs, of altered cellular energetics. In addition, cessation of flow impairs the incoming transfer of nutrients such as glucose, and cells must depend on their own intracellular stores of carbon radicals, if available. Epidemiologic data suggest that there are deleterious effects of hypoxia on the immune system and that these effects result in increased susceptibility to infection. The histology of ischemic tissues demonstrates intravascular neutrophil (PMN) accumulation, vascular damage, and increased vascular permeability. Expression of PMN adhesion receptors is increased when oxygen is nearly completely removed from the medium. Expression of integrins on the cell surface is regulated by intracellular calcium; hypoxia causes a sustained and prolonged increase of intracellular calcium levels. Because both granule movement and functional expression of adhesion receptors on the cell surface are important in leukocyte motility, chemotaxis, and phagocytosis, these functions may be impaired by hypoxia. Exposure of a human macrophage cell line to nonlethal levels of hypoxia causes in vitro release of significant amounts of biologically active cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1 and IL-8, as well as expression of intercellular adhesion molecule-1 and bound and soluble receptors for TNF alpha. Hypoxia markedly decreases T-lymphocyte IL-2 messenger RNA, a key cytokine responsible for B-cell proliferation and immunoglobulin secretion.
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PMID:Leukocyte responses to hypoxic/ischemic conditions. 877 94

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1), CD11a, CD11b, CD18, endotoxin, and various inflammatory cytokines to clarify the relationship between adhesive molecules and cytokines in sepsis. We studied 21 patients with sepsis (sepsis group) and 13 patients with trauma not complicated by infection (trauma group). The mean sICAM-1 level was significantly higher in the sepsis group than in the trauma group. No significant difference was observed in the CD11a, CD11b, and CD18 levels between the two groups. The sICAM-1 levels significantly correlated with the levels of endotoxin, tumor necrosis factor alpha (TNF-alpha), and IL-8, but CD11a, CD11b, and CD18 levels did not correlate with endotoxin or cytokine levels. These findings suggest that ICAM-1 production is induced by endotoxins and cytokines produced in excess by inflammatory reactions and that endotoxins and cytokines are involved in qualitative, but not quantitative changes in LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18).
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PMID:Changes in adhesion molecule levels in sepsis. 882 72

In the present study we evaluated the haematological and immunological changes in 4 patients with advanced melanoma and 6 patients with advanced renal cell carcinoma treated with subcutaneous interleukin (IL)-2 and interferon (IFN)-alfa-2b. Serum samples taken before and during six weeks' courses of IL-2 plus IFN-alfa were assayed for the presence of IL-2, soluble IL-2-receptor (sIL-2R), soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 and IL-8. In addition, whole blood counts were taken. Eosinophilia occurred in all patients, lymphocytosis in 8 patients. The higher maximum level of IL-2 during treatment seemed to be connected to longer survival: it was a median of 578 pg/ml in the patients with a median survival of 7 months, and 1025 pg/ml in the patients who survived a median of 15 months. Conversely, an increase in sIL-2R was an unfavourable sign: it was a median of 8-fold and 3-fold in the patients with a median survival of 7 and 16 months, respectively. During treatment, sICAM-1 levels paralleled with those of sIL-2R. There was major intraindividual and interindividual variation in serum IL-6 and IL-8 levels with no distinctive kinetic pattern. Thus, no definite conclusions could be drawn. However, it seems worthwhile to measure IL-2, sIL-2R and sICAM-1 during immunotherapy; their prognostic value should be further evaluated in a larger patient population.
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PMID:Serum levels of interleukins 2, 6 and 8, soluble interleukin-2 receptor and intercellular adhesion molecule-1 during treatment with interleukin-2 plus interferon-alfa. 887 89

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.
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PMID:Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. 888 Jan 12

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).
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PMID:Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators. 890 94

There is persistent excessive production of a number of pro-inflammatory cytokines in patients with rheumatoid arthritis (RA). A number of experimental therapies have been found to be effective in the treatment of RA, although the effects of these therapies on cytokine production have not been evaluated. One such experimental therapy involves administration of a MoAb to intercellular adhesion molecule-1 (ICAM-1) that has been shown to be clinically beneficial in approximately 60% of the patients, with some patients responding for up to 11 months. The current studies were carried out to determine whether the success of this therapy was associated with changes in mRNA levels for pro-inflammatory and other monocyte-derived cytokines in peripheral blood mononuclear cells (PBMC). Cytokine mRNA levels were assessed in freshly isolated unstimulated PBMC by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) after minimal in vitro manipulation of the cells. Anti-ICAM-1 MoAb administration was followed by an increase in IL-1 beta, IL-8, and tumour-necrosis factor-alpha (TNF-alpha) mRNA detected at 2 or 24 h after the initial infusion in the clinical responders, but no persistent change in these cytokine mRNA levels were observed that correlated with clinical benefit. By contrast, IL-6 mRNA levels declined immediately after the first MoAb infusion and reached pretreatment values variably after the 5 day treatment course. IL-6 mRNA levels remained significantly reduced in patients responding to therapy 1 months after treatment. Fluctuations in monocyte numbers within the PBMC after treatment did not account for the observed changes in cytokine mRNA levels. The results suggest that a decline in IL-6 mRNA levels is a pharmacological action of the MoAb to ICAM-1. Moreover, persistently diminished IL-6 mRNA levels induced by anti-ICAM-1 MoAb might be associated with the long-term benefit of this therapy. In addition, monitoring the activation status of monocytes in circulating PBMC may be useful in predicting response to therapy and warrants further investigation in a larger study population.
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PMID:Persistent reduction in IL-6 mRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis after treatment with a monoclonal antibody to CD54 (ICAM-1). 891 62


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