UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8 and interferon gamma (IFN-gamma), were investigated and the reports on intraocular expression of cytokines, such as TNF, IL-2, IL-6 and IFN-gamma, during uveitis. The exact contribution of these mediators to uveitis remains to be determined. This may provide new clues in the treatment of uveitis.
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PMID:Cytokines and uveitis, a review. 150 1

A coherent view of the role of cytokines in inflammatory eye disease is emerging as a result of studies both in man and experimental animals. Cytokines have been demonstrated in ocular tissue obtained from patients with intraocular inflammation (uveitis) (gamma interferon, IL-2) and have been shown to induce inflammation in experimental animals after intraocular injection [(IL-1, IL-6, IL-8, tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF)]. Several unique features of the immunology of the eye such as the immunosuppression associated with anterior chamber associated immune deviation (ACAID) may be due to the effects of cytokines. Similarly, common complications of ocular inflammation such as glaucoma, keratic precipitates, retinal (macular) oedema and neovascularization may be mediated by cytokines. Understanding of the role of cytokines in inflammatory eye disease has the potential to lead to the development of therapies to abrogate the effects of these important mediators of the inflammatory response.
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PMID:The role of cytokines in the pathogenesis of inflammatory eye disease. 161 54

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.
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PMID:Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells. 761 19

We have characterized the rat LECAM-1 (L-selectin) by the use of newly generated hamster anti-rat LECAM-1 monoclonal antibodies (mAb) (HRL1, HRL2, HRL3, HRL4), with respect to the biochemistry, cellular distribution and function, and developed an ELISA system to detect the soluble form of rat LECAM-1. In the rat, lymphocyte and neutrophil LECAM-1 have apparent molecular masses of 65 and 62 kDa, respectively, and differential glycosylation may account for the molecular heterogeneity. Readily detectable levels of LECAM-1 are expressed on peripheral blood lymphocytes and neutrophils, but not on thymocytes. Lymphocyte LECAM-1 is rapidly shed from the cell surface upon cell activation with PMA, but not with interleukin (IL)-8. In contrast, neutrophil LECAM-1 showed rapid shedding upon stimulation with phorbol 12-myristate 13-acetate (PMA) or IL-8. Concomitantly there is up-regulated expression of Mac-1 in PMA- and IL-8-stimulated neutrophils. Neutrophil rolling in mesenteric venules was significantly inhibited by administration of function-blocking anti-rat LECAM-1 mAb HRL3, but not by non-blocking HRL4, indicating that LECAM-1 plays a significant role in leukocyte rolling. Given that LECAM-1 is rapidly shed from the cell surface, we attempted to develop an ELISA system for detecting LECAM-1 is soluble form, and measured the levels in experimental autoimmune uveitis. The circulating levels of LECAM-1 increased from day 4, which preceded the appearance of clinical signs of uveitis and remained high until uveitis subsided, suggesting that soluble LECAM-1 is potentially a useful parameter to monitor certain types of inflammatory or immune disorders.
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PMID:Characterization of rat LECAM-1 (L-selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM-1 in rat sera. 769 Mar 24

The immunopathology of human T cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 out of 94 (59%) or 13 out of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3+ CD4+ CD8- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA, nucleotide sequence, virus-associated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis.
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PMID:Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production. 786 Jul 69

Human T-cell lymphotropic virus type I (HTLV-I) is known to cause adult T-cell leukemia/T-cell lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recent seroepidemiologic, clinical, and virologic studies indicate that the virus is also related to a certain type of uveitis, which has been classified as uveitis without defined etiologies or idiopathic uveitis. According to the seroepidemiologic survey, the seroprevalence of HTLV-I in patients with idiopathic uveitis was significantly higher than that of two control groups, that is, patients with uveitis with defined etiologies and patients with nonuveitic ocular diseases. Clinically, the uveitis seen in HTLV-I carriers is characterized by moderate to severe cellular infiltration in the eye and by moderate retinal vasculitis, and the intraocular inflammation responds well to corticosteroid therapy. Interestingly, 25% of female patients with the disease had a previous history of Graves disease with hyperthyroidisms. The following virologic, molecular biologic findings suggest that cytokines produced by HTLV-I-infected T cells in the eye play the central role in the pathogenic mechanisms of the uveitis: (a) the virus load in the peripheral blood monocytes analyzed by the quantitative polymerase chain reaction methods was significantly greater in patients with the uveitis than in asymptomatic carriers, (b) the proviral DNA of HTLV-I and the gene expression of the virus at the mRNA level was detected in the infiltrating cells from the eyes of the patients, (c) the virus particles were detected by electron-microscopic examination in the T-cell clones established from the intraocular fluid of the patients, and (d) the HTLV-I-infected T cells produced a variety of cytokines without any stimuli, such as interleukin (IL)-1 alpha, IL-2, IL-3, IL-6, IL-8, IL-10, tumor necrosis factor alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Based on the seroepidemiologic, clinical, and virologic data, the uveitis seen in HTLV-I carriers is considered to be a distinct clinical entity related to HTLV-I infection, and the disease is designated as HTLV-I uveitis.
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PMID:HTLV-I uveitis. 879 4

The present study was designed to investigate the in vitro effects of potential therapeutic agents on cytokine production by five HTVL-I-infected T cell clones (TCC) established from the ocular fluid of patients with HTLV-I uveitis. Each of the five HTLV-I-infected TCC was cultured at 1 x 10(6) cells/ml with or without an immunosuppressive agent (hydrocortisone, FK506, rapamycin, indomethacin, or prostaglandin E2) for 22 hr in humidified 5% CO2 in air at 37 C. The production of various cytokines in the culture supernatant from each TCC was measured by ELISA. The HTLV-I-infected TCC produced high amounts of IL-1 alpha, IL-3, IL-6, IL-8, TNF-alpha, IFN-gamma, and GM-CSF, and low but significant levels of IL-2 and IL-10 without any stimuli. Hydrocortisone severely depressed the production by these TCC of all the cytokines except for IL-2, which was slightly increased. Prostaglandin E2 depressed the production of IL-1 alpha, while it up-regulated the production of IL-6, TNF-alpha, and IFN-gamma. Rapamycin depressed the production of IL-6 and TNF-alpha, and FK506 depressed the production of TNF-alpha. Hydrocortisone also severely depressed the cytokine production by PHA-stimulated peripheral blood mononuclear cells obtained from healthy volunteers. Of the immunosuppressive agents tested, hydrocortisone exhibited the strongest suppression of cytokine production by HTLV-I-infected TCC. This result was in agreement with the in vivo effects of hydrocortisone in patients with HTLV-I uveitis. These TCC will be useful in investigating the effects of potential therapeutic agents for HTLV-I uveitis in vitro.
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PMID:In vitro effects of immunosuppressive agents on cytokine production by HTLV-I-infected T cell clones derived from the ocular fluid of patients with HTLV-I uveitis. 880 2

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
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PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

The capacity of T cells to produce cytokines was investigated using T-cell clones (TCCs) established from infiltrating cells in the aqueous humor (AH) or peripheral blood mononuclear cells (PBMC) of patients with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis. The cytokines produced and tested in the study were interleukin (IL)-1alpha, IL-6, IL-8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte monocyte colony stimulating factor (GM-CSF). All TCCs (n = 9) from AH of VKH patients spontaneously produced significantly larger amounts of IL-6, IL-8, and IFN-gamma than TCCs from healthy donor PBMC. All TCCs (n = 9) from AH of the sarcoidosis patient spontaneously produced significantly larger amounts of IL-1alpha, IL-6, and IL-8 than TCCs from healthy donor PBMC. In addition, the effects of antiinflammatory drugs on the cytokine production by the TCCs were investigated. Hydrocortisone significantly suppressed the production of IL-6, IL-8, and GM-CSF by TCCs from AH of VKH patients. Tacrolimus also significantly suppressed the production of IL-8 and GM-CSF by the TCCs. FTY720, an experimental drug, suppressed only GM-CSF production by TCCs from AH of VKH patients. Diclofenac failed to suppress the production of any cytokines by any TCCs. All tested drugs did not suppress the production of cytokines by TCCs from the sarcoidosis patient. These results thus suggest that cytokines produced by T cells infiltrating in the eye may play an important role in the pathogenesis of uveitis.
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PMID:Cytokine production by T cells infiltrating in the eye of uveitis patients. 974 65

Intravitreal injection of lipopolysaccharide (LPS) induces leukocyte infiltration and protein leakage into the aqueous humor. In the present study, we investigated the role of IL-8 and MCP-1 and regulation of these chemokines by TNFalpha and IL-1 in LPS-induced uveitis in rabbits. After intravitreal injection of LPS, generation of IL-8 in the aqueous humor showed a biphasic pattern with the first peak at 12 hr and the second one at 24 hr, while MCP-1 was produced in a monophasic pattern and peaked at 24 hr. Immunohistochemistry showed that ciliary epithelial cells and infiltrating leukocytes were the producing cells of IL-8 and MCP-1. Administration of anti-IL-8 IgG suppressed by 66% the peak levels of LPS-induced aqueous neutrophil counts at 24 hr but did not suppress aqueous mononuclear cell counts or protein levels. anti-MCP-1 IgG inhibited aqueous mononuclear cell counts by 41% and protein levels by 28%, but did not inhibit aqueous neutrophil counts. The levels of LPS-induced aqueous IL-8 and MCP-1 at 12 hr were inhibited by anti-TNFalpha mAb but not by an IL-1 receptor antagonist (IL-1Ra), while concentrations of the two chemokines at 24 hr were inhibited by both anti-TNFalpha mAb and IL-1Ra. A combination of anti-TNFalpha mAb and rrIL-1Ra had an additive effect on the 24 hr-chemokine levels and inhibited up to 90% chemokine production. Taken together, our results show that IL-8 mediates neutrophil infiltration, while MCP-1 mediates mononuclear cell infiltration and protein leakage in LPS-induced uveitis in rabbits. Levels of aqueous IL-8 and MCP-1 at 12 hr are regulated by TNFalpha, while levels at 24 hr are regulated by TNFalpha and IL-1.
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PMID:Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits. 1007 41

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