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 formylpeptide (fMLP) and C5a chemoattractants were previously shown to cross-desensitize each other's ability to mobilize Ca2+ in leukocytes but not to affect nonchemoattractant Ca(2+)-mobilizing receptors, and vice versa. Our data show that all receptors studied underwent homologous desensitization. Interestingly, peptide chemoattractants (fMLP, C5a, and IL-8) desensitized each other's Ca(2+)-mobilizing responses, but had no effect on a Ca(2+)-mobilizing purinergic receptor. Lipid chemoattractant receptors (PAF and leukotriene B4) were also desensitized by peptide chemoattractants but not vice versa. In the presence of cytochalasin B, only fMLP and C5a caused the activation of phospholipase D in intact leukocytes and enhanced desensitization of IL-8 and C5a but not fMLP receptors. To measure receptor/G protein interactions, agonist-stimulated GTP gamma S binding to leukocyte membranes was measured. Whereas all peptide receptors underwent homologous desensitization, C5a and IL-8, but not fMLP, receptors were cross-desensitized by other peptide chemoattractants. Furthermore, PMA caused inhibition of C5a- and IL-8- but not fMLP-stimulated GTP gamma S binding. These data suggest that in addition to homologous desensitization, peptide chemoattractant receptors cross-desensitize one another by at least two processes. One can be detected at the level of receptor/G-protein interaction and possibly involves receptor phosphorylation by protein kinase C. The fMLP receptor is resistant to this process. The second process is distal to receptor/G-protein interaction and utilizes an undefined pathway to cross-desensitize the Ca2+ mobilization response to all peptide chemoattractants. We propose that receptor cross-desensitization in leukocytes is orchestrated at several levels by mechanisms with selectivity for types of chemoattractant receptors.
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PMID:Cross-desensitization of receptors for peptide chemoattractants. Characterization of a new form of leukocyte regulation. 808 98

Human neutrophils were exposed to the chemotactic factors C5a, FMLP, IL-8, leukotriene B4, and PAF, for 30 s, and subsequently analyzed for protein tyrosine phosphorylation by immunoblotting whole cell lysates with a polyclonal antiphosphotyrosine Ab. All chemotactic factors caused the rapid de novo tyrosine phosphorylation of a broad band of approximately 120 kDa and increased the phosphotyrosine content of several other proteins, including two with molecular masses of 60 and 56 kDa that were present in the unstimulated neutrophil. Tyrosine phosphorylation was evident as early as 10 s after stimulation and was maintained for 1 to 3 min before dephosphorylation occurred. The extent of tyrosine phosphorylation was dependent on the concentration of chemotactic factor, with stimulation observed at concentrations as low as 10 to 100 nM. To investigate the pathway used by chemotactic factors to transduce this signal, neutrophils were treated with PMA. PMA also stimulated tyrosine phosphorylation in the neutrophil but with a slower response time and a different pattern of affected proteins. Additional experiments suggested that tyrosine phosphorylation is involved in the regulation of the neutrophil respiratory burst because the tyrosine kinase inhibitor, herbimycin A, inhibited C5a-induced protein tyrosine phosphorylation and also prevented C5a- and FMLP-induced superoxide anion production. Herbimycin A also inhibited PMA-induced tyrosine phosphorylation and superoxide anion production. To confirm that the ability to stimulate tyrosine phosphorylation was intrinsic to the C5a receptor, tyrosine phosphorylation was examined in both undifferentiated U937 cells (C5a receptor negative) and cAMP differentiated U937 cells (C5a receptor positive). C5a induced tyrosine phosphorylation only in differentiated U937 cells. Analysis of the C5a receptor mRNA using the PCR confirmed its presence in differentiated and its absence in undifferentiated U937 cells. Therefore, C5a stimulates tyrosine phosphorylation via a receptor-mediated mechanism and U937 cells provide a system in which G-coupled receptor-mediated tyrosine phosphorylation can be investigated.
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PMID:C5a as a model for chemotactic factor-stimulated tyrosine phosphorylation in the human neutrophil. 813 59

The authors studied the inflammation's factors of the lung in six asthmatic children in BAL liquid. Were monitored either the cells either the inflammation's mediators as PCF--albumin--PGE2--PG1 alpha--Tx beta 2--PAF--LT beta 4 and the interleukines IL1 alpha--IL-1 beta--IL-6--IL-8. In the BAL liquid was observed the macrophagic non epiteliomorphic and lymphocytic preminence. The mediators of inflammation were all increased in particular IL-1 beta--IL-6--IL-8. The cultural exams were negatives in 80% of children.
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PMID:[The correlations between chemical mediators and interleukins in the bronchoalveolar lavage fluid in 6 asthmatic children]. 832 21

Human erythroid progenitor cells grown in a suspension culture system were used to study possible interactions between different guanine nucleotide-binding protein (G-protein)-coupled receptor-effector systems during normal cell differentiation. Agonist-stimulated adenylyl cyclase was not inhibited by any one of a panel of ligands (ADP, UTP, platelet-activating factor, thrombin, alpha2-adrenoceptor agonists, interleukin 8, lysophosphatidic acid) most of which are known, in other cells, to reduce cAMP formation by a Gi-mediated, pertussis toxin-sensitive mechanism. The first four of these ligands are also known to cause transient changes in intracellular [Ca2+] in erythroid cells. Rather than inhibiting, thrombin (but not ADP, UTP or PAF) specifically caused a fivefold increase in the maximum adenosine- or prostaglandin E1-stimulated cAMP formation, without any shift of the concentration/response curves. Thrombin did not enhance forskolin- and AlF4-stimulated cyclase activity and had only a marginal effect on isoprenaline-dependent stimulation. The effect of thrombin seemed to be unrelated to intracellular Ca2+ release but could be partially mimicked by phorbol ester (PMA)-induced stimulation of protein kinase C (PKC) and was inhibited by staurosporin or by inactivation of PKC after long-term incubation with PMA. The activity of thrombin was restricted to proliferating, colony-forming progenitor cells while proerythroblasts were completely unresponsive. Our results suggest that the interaction of thrombin with Gs-linked receptors requires phosphorylation of a target protein that is different from adenylyl cyclase, Gs or Gi but may be involved in the regulation of receptor desensitization.
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PMID:Crosstalk between thrombin and adenylyl cyclase-stimulating agonists in proliferating human erythroid progenitor cells. 875 Sep 12

N-formyl-methionyl-leucyl-phenylalanine (fMLP), a bacterial derivative, induces and modulates various cellular responses linked to inflammation. In this work we evaluated the impact of fMLP stimulation on three pro-inflammatory cytokines: IL-1 alpha, IL-1 beta and IL-6. We found that fMLP induces the secretion of IL-1 alpha, IL-1 beta and IL-6 in human peripheral blood mononuclear cells (PBMC). It also increased LPS-induced secretion of these three cytokines. Northern blot analysis demonstrated that fMLP induced IL-1 alpha, IL-1 beta and IL-6 gene expression by human PBMC. The fMLP-induced IL-1 alpha and IL-1 beta gene expression and IL-6 secretion were abolished by pertussis toxin pretreatment, which suggests that the fMLP induction of cytokine was also mediated via a Gi protein. The concentration range of fMLP used to obtain these effects, in a dose dependent fashion, was 20 microM to 1100 microM. The mechanism by which fMLP modulates cytokine secretion is still not characterized. fMLP seems to share similar biological activities with other chemotactic factors (C5a, MCP-1, PAF, IL-8) that are able to modulate cytokines, and whose receptors belong to the same superfamily as the fMLP receptor(s).
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PMID:N-formyl-methionyl-leucyl-phenylalanine induces and modulates IL-1 and IL-6 in human PBMC. 881 43

Neutrophil recruitment from the blood stream into the airways is one of the important features of many inflammatory disorders in the lung. In this process, neutrophils migrate first from the blood across the ECs in the apical-to-basolateral direction into the tissues and then across airway epithelium in the basolateral-to-apical direction into the lung lumen. We investigated and compared the different mechanisms of neutrophil transmigration in vitro across monolayers of these two cell types in both directions. Neutrophil migration induced by chemoattractants was stronger across resting EC than across resting epithelial cells when both cell types were growing on top of the filters (i.e., migration in the apical-to-basolateral direction). Much higher neutrophil transepithelial migration was found in the physiological, basolateral-to-apical direction (cells hanging underneath the filters) than in the opposite direction across either resting or IL-1 beta-activated epithelial cells. In contrast, no significant difference was observed with EC under these conditions. After a 4-h IL-1 beta activation, neutrophil migration across EC was dependent on IL-8 and PAF. However, the migration across epithelial cells relied, to a greater extent, on IL-8 production, and not on PAF. The adhesion molecule ICAM-1 contributed much less to neutrophil migration across epithelium than that across endothelium. Our study provides evidence of different mechanisms of neutrophil transmigration across monolayers of EC and epithelial cells in vitro, indicating that different processes control neutrophil transmigration across EC and epithelial cells in vivo.
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PMID:Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms. 890 8

Multiple organ dysfunction syndrome (MODS) is a critical condition developing in the patients under overwhelming surgical insults such as a major surgery, severe trauma, extensive burn, and systemic sepsis. The host response to those surgical insults is the main pathogenetic factor contributing to the development of shock and MODS seen in surgical patients. The proinflammatory cytokines, TNF-alpha (TNF) and interleukin-1 beta (IL-1), are known to play a pivotal role in the pathogenetic mechanisms of MODS. In response to surgical insults, macrophages produce and release TNF and IL-1 which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators (growth factors, adhesion molecules, complement cleavage products, thrombin, eicosanoids, PAF, nitric oxides, oxygen-free radicals, granulocyte elastase, etc.) The resultant systemic inflammation may develop into shock and MODS when the primary insults are overwhelming (early MODS) or a second inflammatory insult such as sepsis triggers an exaggerated inflammation. In the patients suffering from MODS, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines induce an autodestructive generalized inflammatory reaction. This condition is termed "Cytokine Storm" by the author. In the cytokine storm, not only proinflammatory cytokines but also anti-inflammatory cytokines are elevated in the blood stream. With the recent understanding of the biological and pathological roles of cytokines and other mediators, a new therapeutic strategy has been developed. In addition to the reduction of the surgical insults, a variety of anti-cytokine therapy and anti-mediator therapy has been tested in an attempt to prevent or treat the life-threatening MODS.
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PMID:[Cytokine storm in the pathogenesis of multiple organ dysfunction syndrome associated with surgical insults]. 894 Jun 90

Ulcerative colitis involving primarily the mucosa of the colon and rectum is a diffuse and nonspecific inflammatory disease. Immunocompetent cells infiltrating in the inflammed mucosa are mainly lymphocytes, macrophages and neutrophils. These activated cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8 and TNF alpha and inflammatory activators such as PAF, leukotriene, prostaglandins, free radicals and proteases, resulting in acute on chronic states. Non-surgical therapy for ulcerative colitis includes basic medical therapy with sulfasulphapyridine, 5-ASA, corticosteroids and immune suppressive drugs as well as new therapies, which are leukocytapheresis, granulocytapheresis, anticytokine therapy with antiTNF alpha monoclonal antibody, IL-1ra and IL-10, intravenous treatment of massive immunoglobulins and transdermal nicotine therapy.
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PMID:[Non-surgical therapy for ulcerative colitis]. 916 97

Immunoglobulin E plays a central role in the pathogenesis of allergic diseases. Therefore an understanding of mechanisms which regulate production of IgE is very important. Recent studies have demonstrated that the induction of IgE synthesis in B cells requires two signals. The first one, IgE isotype-specific, is delivered by interleukins 4 or 13 and results in epsilon germ line transcription. The second B-cell-activating factor is responsible for switch recombination and expression of mature epsilon RNA transcripts. This signal is delivered by lymphocytes T, but these cells can be replaced by Epstein-Barr virus infection, protein gp39 (CD40L), monoclonal antibodies to CD40 and CD58, membrane-TNF-alpha, as well as corticosteroids. Besides this a variety of factors can modulate the IgE synthesis. Interleukin-2, -5, -6, -9, -10, MIP1-alpha, RANTES and sCD23 enhance the production of IgE whereas PAF, PGE2, IL-8, -12 and 18, IFN-alpha and gamma, TGF-beta, sIL-4R, IL-1Ra, and probably sIL-1R inhibit it. In this article, we review current knowledge about the mechanisms underlying the synthesis of IgE in humans, including molecular events and clinical attempts at reduction of the total IgE level in patients with allergic diseases.
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PMID:[Regulation of immunoglobulin E synthesis]. 948 97

While it is clear that the clinical expression of IgE-mediated diseases depends upon the actions of multiple mediators, histamine, the earliest recognized mediator of allergy, remains a prominent contributor. Histamine released from mast cells binds to specific receptors (H1, H2, H3) to produce its clinical effects. The cardinal features of asthma include smooth muscle spasm, mucosal edema, inflammation and mucus secretion. It has been demonstrated that two of these features, bronchospasm and mucosal edema, can be caused by H1-receptor stimulation, while H2- and possibly H1-activation are probably minor causes of mucus secretion. Histamine interacts directly with the endothelial cells (EC) and induces permeability, a transient expression of P-selectin and the secretion of lipid mediators (e.g. PGI2, PAF and LTB4). Moreover, histamine induces a significant increase of IL-6 and IL-8 secretion by EC. Since IL-8 exerts a chemotactic activity for neutrophils, eosinophils and basophils, and IL-6 is involved in endothelium permeability, the secretion of cytokines may be involved in the late phase reaction. Some antihistamines (i.e., levocabastine, terfenadine, loratadine, azelastine and oxatomide) can reduce ICAM-1 expression. The participation of histamine in the allergic inflammation, including asthma, must be re-examined, since the effects of histamine are more widespread.
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PMID:[Histamine in the pathogenesis of asthma]. 961 6


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