Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on our earlier data on the enhancing effect of histamine on the action of interleukin-6 (IL-6), we have studied the molecular mechanisms of these interactions. The effect of histamine was investigated on the binding of 125I-IL-6 by B lymphoma cell line CESS, monocytoid cell line U937 and hepatoma cell line HepG2. Histamine increases the IL-6 binding by CESS cells and inhibits that by U937 and HepG2 cells. Using H1 receptor (cetirizin and loderix) and H2 receptor (cimetidine and ranitidine) specific antagonists, an H1-dependent stimulation of IL-6 binding by CESS cells was found. In contrast, down-regulation of IL-6 binding by histamine was clearly mediated through H2 receptors. On U937 cells, using a monoclonal antibody reacting with the 80 kd chain of the human IL-6 receptor, and H2-receptor mediated inhibition of IL-6 receptor expression was found by FACS analysis.
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PMID:Histamine influences the expression of the interleukin-6 receptor on human lymphoid, monocytoid and hepatoma cell lines. 168 Feb 74

Epithelial cells are likely to modulate inflammation and tissue repair in the airways, but the factors responsible for these processes remain unclear. Because human airway epithelia are infrequently available for in vitro studies, transformed epithelial cell lines are of interest as models. We therefore investigated the response of an SV-40/adenovirus-transformed human bronchial epithelial cell line (BEAS-2B) to histamine, a mediator with relevance for airway diseases. The intracellular calcium response to histamine (10(-4) M) was measured, using Fura-2 and microspectrofluorimetry. Histamine induced a transient increase in intracellular calcium that originated from intracellular sources; this effect was inhibited by the H1 receptor antagonist diphenhydramine, suggesting that BEAS cells retain functioning histamine receptors. BEAS cells were grown to confluence on microporous, collagen-coated filters, allowing measurement of vectorial release of soluble mediators. Monolayers exposed to histamine for 30 min released interleukin-6 and fibronectin in the apical direction, in a dose-dependent manner. Little eicosanoid production was induced by histamine, either in the apical or the basolateral direction, although BEAS cells constitutively produced small amounts of prostaglandin E2 and 15-HETE. However, these cells formed large amounts of eicosanoids in response to ozone exposure as a positive control. Comparison of our data with published reports for human airway epithelia in primary culture suggests that the BEAS cell line is, in a number of respects, a relevant model for the study of airway epithelial responses to a variety of stimuli.
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PMID:The response of a human bronchial epithelial cell line to histamine: intracellular calcium changes and extracellular release of inflammatory mediators. 193 Oct 77

Mast cells produce a number of cytokines including IL-6. In view of the large amounts of de novo synthesis induced by the activation of rat peritoneal mast cells and previous observations of expression of this cytokine by human lung mast cells, we have studied the regulation of IL-6 production. We examined the hypothesis that mast cell IL-6 production is not related to previous histamine release. Highly purified rat peritoneal mast cells were activated with anti-IgE, calcium ionophore A23187, or LPS. Histamine was used as a marker of preformed mediator release and IL-6 production was assessed by using the B9 hybridoma growth factor bioassay. Anti-IgE activation of rat peritoneal mast cells induced IL-6 production and histamine release. In contrast, LPS activation induced substantial, serum-dependent, IL-6 production without a significant level of histamine release. No preformed IL-6 was detected in the cells. Calcium ionophore induced histamine release from mast cells to a greater extent than did anti-IgE, but no A23187-induced IL-6 production was observed. A23187-treated cells retained high viability and produced a significant amount of TNF-alpha. To further examine the concordance of IL-6 production and histamine release we used mast cell stabilizing drugs. Dexamethasone and nedocromil significantly inhibited IL-6 production in response to anti-IgE. Our results demonstrate that there is not a direct relationship between mast cell degranulation and IL-6 production. Our observations are important for understanding the role of mast cells in inflammation and for developing strategies to modulate mast cell function in disease.
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PMID:IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. 751 39

Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD. In the present study, glial fibrillary acidic protein-positive human U373MG astrocytoma cells were used as a model of reactive astrocytes. Production of IL-6 in response to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM), substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM) stimulated the release of IL-6 in a time- and concentration-dependent manner, with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for these agents. Both histamine and SP enhanced the formation of inositol phosphates and increase intracellular calcium levels, suggesting that the phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL-1 beta, which produces a much more robust release of IL-6 than histamine or SP, has no effect on inositol phosphate formation or intracellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the release of interleukin-6 from human astrocytoma cells. 751 68

Airway epithelial cells have a potential to produce cytokines which are relevant to airway inflammation. To elucidate the mechanisms of their regulation, we focused on the effects of three chemical mediators [histamine, platelet-activating factor (PAF) and endothelin-1] important in the pathogenesis of bronchial asthma. Histamine, but not PAF or endothelin-1, showed a dose-dependent stimulatory effect on the release of interleukin-6, interleukin-8 and granulocyte-macrophage colony-stimulating factor by normal and transformed human bronchial epithelial cells when studied 6 h after the treatment. The process required protein synthesis as evaluated by the effect of cycloheximide, and was mainly via H1 receptor. We concluded that histamine might be involved in the activation of airway epithelial cells to release inflammatory cytokines in allergic responses.
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PMID:Histamine activates bronchial epithelial cells to release inflammatory cytokines in vitro. 758 Feb 91

An enhancing effect of histamine on the biosynthesis and gene expression of interleukin-6 (IL-6) by human cell lines, Epstein-Barr virus (EBV)-infected human B lymphoma line BMNH and the glioblastoma line SK-MG4 has been found. No similar effect of histamine has been detected on the IL-6 production by any other B-cell line, CESS or human peripheral monocytes. Histamine stimulates the IgM production of BMNH cells by autocrine action of IL-6 induced by histamine, since either neutralization of IL-6 by polyclonal antibody or blocking the IL-6 receptor by specific monoclonal antibody abolished the effect of histamine.
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PMID:Interleukin-6 biosynthesis is increased by histamine in human B-cell and glioblastoma cell lines. 847 12

Bioactive substances in fresh frozen plasma (FFP) are considered to be related to adverse reactions after transfusion, particularly in septic or traumatized patients. Therefore, we analysed the concentration of various bioactive substances (histamine, eosinophil cationic protein, eosinophil protein X, myeloperoxidase and interleukin-6) in 25 u. of thawed FFP from healthy donors. These were compared with donor plasma concentrations of 24 healthy controls. In addition, we analysed the concentration of the bioactive substances, except interleukin-6, in 25 u. of thawed FFP, which were subjected to leucocyte filtration before freezing and storage. Finally, we analysed the substances in 10 leucocyte non-filtered plasma units before freezing and storage, and after thawing, respectively. Before analyses, which were performed by ELISA and RIA methods, these latter samples were sterile filtered through a 0.20-micron filter. Histamine, eosinophil cationic protein, eosinophil protein X and myeloperoxidase concentrations were significantly greater (P < 0.05) in the 25 u. of FFP compared with normal donor plasma. Pre-storage leucocyte filtration reduced concentrations of the bioactive substances in FFP to concentrations comparable with normal donor plasma concentrations. Interleukin-6 was undetectable in all FFP units and in 21 of the 24 control donors. Histamine, eosinophil cationic protein and myeloperoxidase concentrations were significantly higher (P < 0.05) in samples collected from the 10 u. of FFP after freezing and thawing compared with samples collected before freezing. We conclude that fresh frozen plasma prepared by a conventional separation method contains various leucocyte-derived bioactive substances, which may be reduced by pre-storage leucocyte filtration.
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PMID:Leucocyte-derived bioactive substances in fresh frozen plasma. 917 70

We recently reported on the successful generation of immortalized (CEPI-17-CL4) cells from primary human corneal epithelial (P-CEPI) cells which exhibited phenotypic, immunohistochemical and metabolic characteristics akin to the P-CEPI cells. The aims of the present studies were to investigate the ligand binding and functional coupling of the histamine receptors to various biochemical and physiological systems in the P-CEPI and CEPI-17-CL4 cells and to relate these findings to the normal and/or pathophysiological role of histamine on the human ocular surface. Specific [3H]-pyrilamine binding to CEPI-17-CL4 cell homogenates comprised >93% of the total binding and represented interaction with an apparent single population of high affinity (Kd=3.76+/-0.78 nM; n=4) and saturable (Bmax = 1582+/-161 fmol g(-1) tissue) number of histamine-1 (H1) receptor binding sites on CEPI-17-CL4 cell homogenates. The H1-receptor selective antagonists, pyrilamine (Ki=3.6+/-0.84 nM, n=4) and triprolidine (Ki = 7.7+/-2.6 nM, n=3), potently displaced [3H]-pyrilamine binding, while the H2- and H3-receptor selective antagonists, ranitidine and clobenpropit, were weak inhibitors (K(i)s>13 microM). Histamine induced phosphoinositide (PI) hydrolysis 2.7-4.4 fold above basal levels and with a potency of 14.9+/-4.9 microM (n=9) and 4.7+/-0.2 microM (n=9) in P-CEPI and CEPI-17-CL4 cells, respectively. Histamine-induced PI turnover was antagonized by H1-receptor selective antagonist, triprolidine, with a potency (Ki) of 3.2+/-0.66 nM (n=10) and 3.03+/-0.8 nM (n=4) in P-CEPI and CEPI-17-CL4 cells, respectively, but weakly effected by 10 microM cimetidine and clobenpropit, H2- and H3-receptor antagonists. The PI turnover response was attenuated by pre-treatment of the cells with the selective phospholipase C inhibitor, U73122 (1-(6-((17beta-3-methoxyestra- 1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) (IC50=4.8+/-2.4 microM, n = 3). Histamine stimulated intracellular Ca2+ ([Ca2+]i) mobilization in CEPI-17-CL4 cells with a potency of 6.3+/-1.5 microM (n=4). The histamine-induced [Ca2+]i mobilization was reduced by about 28% following pre-incubation of the cells with 4 mM EGTA. While triprolidine completely inhibited histamine-induced [Ca2+]i mobilization, it did not influence the bradykinin-induced [Ca2+]i mobilization response. Histamine (EC50s = 1.28-2.77 microM, n=3-4) concentration-dependently stimulated the release of interleukin-6 (IL-6), IL-8 and granulocyte macrophage colony-stimulating factor, but it did not significantly alter release of tumour necrosis factor-alpha, PGE2 or collagenase-1 (matrix metalloproteinase-1; MMP-1) from CEPI cells. However, IL-1 (10 ng ml(-1)), foetal bovine serum (10%) and phorbol-12-myristate-13-acetate (3 microg ml(-1)) were effective positive control secretagogues of all the cytokines, PGE2 and MMP-1, respectively, from these cells. It is concluded that the CEPI cells express H1-histamine receptors which are positively coupled to PI turnover and [Ca2+]i mobilization which may be directly or indirectly responsible for the release of various cytokines from these cells at physiologically and/or pathologically relevant concentrations.
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PMID:Pharmacology of [3H]-pyrilamine binding and of the histamine-induced inositol phosphates generation, intracellular Ca2+ -mobilization and cytokine release from human corneal epithelial cells. 986 65

Adverse effects of perioperative blood transfusion appear to be storage-time-dependent and may be related to extracellular accumulation of bioactive substances in blood products. In this study the clinical effects of leukofiltered and non-filtered blood products in patients undergoing surgery for burn trauma are investigated. 24 consecutive patients were randomly selected to receive transfusion with non-filtered blood components (group A, n = 12) or similar products, which were prestorage leukofiltered (group B, n = 12). The burn injury was scored using the Bull and Fischer index of age and burn surface area. Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in plasma or serum collected from all patients 30 min before skin incision, at skin incision and 5, 10 and 30 min and thereafter every 30 min after skin incision until the grafts were secured by wrapping. Samples were also taken 8 h after skin incision and in the morning of postoperative days 1-5. The amount of blood products transfused from admission until day 5 postoperatively was recorded. All patients were followed until discharge or death. The Bull and Fischer index was comparable in the two groups. Prestorage leukofiltration reduced the amount of blood products required for transfusion significantly (p < 0.05) compared with non-filtered products. The levels of the various bioactive substances changed during and after the operation. In particular, ECP and MPO levels increased significantly (p < 0.05) in group A patients compared with unchanged (ECP) or decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma had more severe impact on group B patients than on group A patients. Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce transfusion related accumulation of various bioactive substances and the requirement for blood in burn trauma patients.
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PMID:Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma. 1020 93

Histamine released from dermal mast cells plays a central role in the increased vascular permeability in acute urticaria, and administration of anti-histamines usually suppresses development of wheals. Acute idiopathic urticaria, particularly a severe case, occasionally presents with acute inflammatory reactions such as low-grade fever and leukocytosis and is resistant to anti-histamines. Considering the wide spectrum of proinflammatory cytokines and chemokines that can be released from activated mast cells, some of them might be involved in the pathogenesis of urticaria. We measured plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in 16 cases of severe acute urticaria. None of them showed elevated plasma levels of IL-8 or TNF-alpha. Nine out of 16 acute urticaria patients showed elevated circulating IL-6 with concomitant increases in serum CRP levels. All such patients were resistant to conventional anti-histamine treatment and required systemic steroids for complete suppression of wheal development. After subsidence of the urticaria, their elevated IL-6 and CRP levels dropped to their normal ranges. In contrast, all but one patient without elevated circulating IL-6 was successfully treated with a H1 receptor antagonist, cetirizine. The data suggest involvement of IL-6 in the pathogenesis of severe acute urticaria that is resistant to anti-histamines.
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PMID:Acute urticaria with elevated circulating interleukin-6 is resistant to anti-histamine treatment. 1143 61


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