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)

Cytokines have a central role in the generation of an autoimmune response and can directly affect the target organ. In Graves' disease, both the infiltrating mononuclear cells and the thyroid follicular cells produce certain cytokines, but the relative contribution of each is unclear, and there are conflicting data on the exact profile of cytokines expressed within the thyroid. To clarify these issues, we used the method of reverse transcription-polymerase chain reaction amplification to analyze cytokine gene expression by intrathyroidal lymphocytes (ITL) and purified thyroid follicular cells (TFC) from six patients with Graves' disease. All ITL samples were positive for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF alpha) messenger ribonucleic acids (mRNAs). Four samples were positive for IL-2 mRNA, and of these, three were also positive for interferon-gamma (IFN gamma). All TFC samples contained IL-6 and IL-8 mRNAs, even after depletion of CD3-positive T-cells. One TFC sample was additionally positive for IL-10 and TNF alpha mRNAs, and in the case of IL-10, this signal was not eliminated by CD3-positive T-cell depletion. IL-4 was not detected in any sample of ITL, TFC, or whole tissue. Semiquantitative analysis showed that the ITL fraction represented the major source of IL-6, IL-8, and TNF alpha mRNAs. By contrast, only three of five multinodular goiter samples were positive for IL-1 alpha mRNA; of these, two were also positive for IL-6, and 1 was positive for IL-8 mRNA. One multinodular goiter sample was positive for IL-8 mRNA alone, but IL-2, IL-4, IL-10, and TNF alpha mRNAS were not detected. These results suggest that although the TFC themselves may express certain cytokines, the ITL population represents the most important source of cytokine production in Graves' thyroid glands. The presence of IL-2, IFN-gamma, and TNF alpha and the absence of IL-4 mRNA in samples of ITL indicate a pattern of cytokine production that most closely resembles that of the TH1 helper T-cell subset. Given the etiological role of thyroid-stimulating antibodies in Graves' disease, the production of which is likely to depend upon TH2 helper T-cell function, it is perhaps surprising that the TH1 subset appears to predominate. It is possible that IL-10 is important in stimulating intrathyroidal autoantibody production, and this cytokine may also play a role in inhibiting cell-mediated thyroid injury in Graves' disease.
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PMID:Analysis of cytokine gene expression in Graves' disease and multinodular goiter. 804 47

Endotoxin [lipopolysaccharide (LPS)] is a potent inflammatory stimulus and can activate human umbilical vein endothelium (HUVE) for leucocyte adhesiveness and transendothelial migration. Here we investigated the role of HUVE-secreted cytokines in this process. When HUVE monolayers were grown on filters and preincubated for 3 hr with LPS, 51Cr-labelled polymorphonuclear leucocytes (PMNL) migrated across the HUVE in a dose- and time-dependent manner. Maximal PMNL transmigration with LPS (1 ng/ml) was 26 +/- 3% of added PMNL in 75 min. Neutralizing antibodies to interleukin-1 alpha (IL-1 alpha) and IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-8 or recombinant IL-1 receptor antagonist had no effect on the activation by LPS of the HUVE for supporting migration of PMNL. The HUVE 'activated state' declined with prolonged (22 hr) exposure to LPS, as reflected by a decrease in PMNL transendothelial migration to 5.5 +/- 1% and in the expression of the endothelial cell adhesion molecule, E-selectin, as compared to stimulation with LPS for 3 hr. However, simultaneous exposure to interferon-gamma (IFN-gamma) (200 IU/ml) and LPS maintained maximal PMNL transendothelial migration (28 +/- 4%) for at least 24 hr, prolonged E-selectin expression by HUVE and superinduced intracellular adhesion molecule-1 (ICAM-1) expression. The PMNL transendothelial migration was blocked by > 90% by monoclonal antibody (mAb) to CD18 with either 3 hr of LPS or 22 hr LPS + IFN-gamma stimulation. Migration was partially inhibited by mAb to E-selectin (30-40%) or to ICAM-1 (35-45%) and by a combination of both reagents (50-60%) under both stimulation conditions. Thus, LPS activation of HUVE for PMNL transendothelial migration: (a) does not require secretion of IL-1, TNF-alpha or IL-8 by the endothelium, (b) IFN-gamma enhances and prolongs endothelial activation by LPS and may increase leucocyte infiltration in LPS or bacterial inflammatory reactions, and (c) CD18-dependent mechanisms are equally important for PMNL transendothelial migration under both acute (3 hr) and prolonged (22 hr LPS + IFN-gamma) activation of endothelium.
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PMID:Endotoxin activation of endothelium for polymorphonuclear leucocyte transendothelial migration and modulation by interferon-gamma. 810 89

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

In this study, we demonstrate that mononuclear cells of human milk have a potential for production of many different cytokines. We applied a technique for cytokine detection at the single-cell level using cytokine specific MAb and immunofluorescence. The characteristic staining pattern obtained represents intracellular cytokine production, which allows for the assessment of the cellular origin of production. Milk mononuclear cells were mitogen-stimulated in vitro and cultured for 4 h and then stained for 13 cytokines. Lipopolysaccharide stimulation induced extensive production of the following monokines: IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, and tumor necrosis factor-alpha. IL-10 and granulocyte-macrophage colony-stimulating factor were smaller products, although detectable in most samples. The abundant monokine production correlated with the high number of macrophages in milk. Spontaneous monokine production in unstimulated cells could be detected in six out of 11 samples. The highest incidence was evident for IL-8. No spontaneous lymphokine production was detected. Considering the low proportion of lymphocytes, stimulation with phorbol myristate acetate in combination with ionomycin resulted in considerable production of the following lymphokines: IL-2, IL-3, IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha. Macrophages contributed to the high production of tumor necrosis factor-alpha and GM-CSF. IL-5 synthesis was detectable in only one sample. This work reveals that human milk mononuclear cells are potent producers of cytokines when mitogen stimulated in vitro. The in vivo implications of these findings remain to be investigated further.
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PMID:Cytokine production in mononuclear cells of human milk studied at the single-cell level. 823 27

We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta, IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-alpha was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-alpha was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.
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PMID:PCR detection of cytokines in normal human and pagetic osteoblast-like cells. 825 52

Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN-gamma) may play a role in the treatment of certain respiratory conditions associated with infection and inflammation. This study was designed to determine if rIFN-gamma could be delivered effectively in a group of normal human volunteers. The effectiveness of the inhaled delivery system was demonstrated by the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also showed evidence for up-regulation after rIFN-gamma therapy. Compared with baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores, spirometry, morning peak expiratory flow rate (PEFR), or the response to methacholine. Of interest, the evening PEFR increased significantly (p = 0.02), from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma. Although there was no significant change in total white cell count in BAL fluid, the cellular composition did demonstrate a significant decrease in percentage of alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02) after rIFN-gamma. There were no histologic differences seen in bronchial biopsy specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases.
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PMID:The effects of inhaled interferon gamma in normal human airways. 825 19

Monocyte chemotactic and activating factor (MCAF) is an important mediator of monocyte recruitment to sites of chronic inflammation and neoplasia. In the present study, we determined whether MCAF can also enhance the activation of tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic tumoricidal activity against allogeneic A375 melanoma cells, irrespective of their metastatic potential. The sequence of MCAF and LPS treatment was crucial. Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and then with MCAF were not. Treatment of monocytes with MCAF and LPS also significantly increased production of tumor necrosis factor. These data suggest that like interferon-gamma, MCAF can prime human monocytes to respond to LPS. Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS-triggered tumoricidal response. Collectively, these data show that MCAF can influence the recruitment and tumoricidal activation of blood monocytes. Therefore, MCAF may be an important mediator of tumor regression.
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PMID:Synergism between human recombinant monocyte chemotactic and activating factor and lipopolysaccharide for activation of antitumor properties in human blood monocytes. 826 May 37

Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time-dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL-8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.
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PMID:Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism. 828 50

Cytokines presently known to be involved in systemic bacterial infection are tumour-necrosis factor (TNF), interleukin (IL)-1, IL-6, IL-8 and interferon-gamma (IFN-gamma) and the counterregulatory molecules soluble TNF receptor (sTNFR) and IL-1 receptor antagonist (IL-1 Ra). In animal models TNF, IL-1 and IFN-gamma mediate organ damage, low blood pressure and fatality, whereas IL-6 is involved in infection-related manifestations, like the production of acute-phase protein and fever, and IL-8 is chemotactic to granulocytes. TNF and IL-1 increase expression of adhesion molecules on endothelial cells and influence a number of components of the haemostatic system in favour of coagulation. The presence of cytokines in the circulation is characterized by sequential releases of TNF, IL-1 and IL-6/IL-8; however, many variations of this pattern exist during human infection. In experiments as well as in human infection TNF, IL-1, IL-6, IL-8 and IFN-gamma have been detected, and levels of TNF, IL-6 and IL-8 have been found to be associated with the severity of the disease. Collectively, TNF, IL-1 and IFN-gamma emerge as mediators of systemic infection and septic shock whereas IL-6 and IL-8 are related to other manifestations of infection. Counteracting molecules like sTNFR are released after somewhat of a delay following TNF and IL-1Ra is released concomitantly with IL-1. Probably these factors modulate the cytokine effect although their true potency in natural infection has yet to be clarified. In granulocytopenic infections TNF, IL-1, IL-6 and IL-8 can be detected in serum, and levels of TNF and IL-6 are even higher than in the normal situation in experimental animals. Antibodies to TNF inhibit bacteria-induced fatality in granulocytopenic mice. Altogether, few data related to the granulocytopenic situation are available. However, it is reasonable to believe that the altered development of granulocytopenic infections is due to changes in the cellular constitution and not to changes in cytokine production.
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PMID:Cytokine mediators of septic infections in the normal and granulocytopenic host. 831 84

The influence of pooled human IgG preparations for intravenous use (i.v.Ig) on in vitro-induced cytokine production was studied at the single-cell level using cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescent technique. Cultured mononuclear cells from peripheral blood from healthy adult donors were polyclonally stimulated for 96 hr by either direct ligation of T-cell receptors using immobilized anti-CD3 mAb or by a combination of a protein kinase C activator [phorbol 12-myristate 13-acetate (PMA)] and a calcium ionophore (ionomycin) in the absence or presence of i.v.Ig. A marked inhibition of proliferation and blast transformation was noted in all i.v.Ig exposed cultures, despite good cell survival. The production of the T-cell lymphokines interleukin-2 (IL-2), IL-10,interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) was significantly down-regulated during the whole studied period in the i.v.Ig containing anti-CD3 stimulated cultures. The synthesis of the monokine IL-8 was not suppressed and that of TNF-alpha, which was made by both lymphocytes and monocytes, was only moderately inhibited. Somewhat different and more transient effects were observed in the i.v.Ig-exposed PMA/ionomycin-activated cultures. The production of IL-2, IL-3, IL-4, IL-5, IL-10, TNF-beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) was down-regulated during the initial phase of the cultures up to 48 hr, but not at 48-96 hr. The synthesis of IFN-gamma and TNF-alpha was unaffected of the influence of i.v.Ig during the entire culture period. The expression of IL-2 receptors (IL-2R) was significantly suppressed in the i.v.Ig-treated anti-CD3-activated cells, but not in the PMA/ionomycin-stimulated cultures. Taken together our results indicate that pooled IgG may mediate immunomodulation by direct effects on cytokine production and on T-cell proliferation.
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PMID:Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG. 834

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