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)

We analysed in mice why the salivary gland extract (SGE-2) from Ornithodoros erraticus and O. moubata induce a protective response with Freund's adjuvants (FAs) in swine while the saliva, in natural conditions, does not. Such protection has been ascribed to the fact that administration of SGE-2 plus FAs permits the recognition of certain salivary components that under natural conditions are not immunogenic. The present findings confirm this hypothesis since in mice, which are unable to recognize the above components, the SGE-2-FAs do not induce any protection. We rule out the possibility that the cause of this could lie in the absence of prostaglandin E2 in the SGE-2 (vs saliva) since it is not present in either fluid. Neither could it be due to a change in antibody isotype since those induced by parasites bites and by the SGE-2-FAs are the same (IgG2a > IgG1 > IgG2b; not IgG3, IgM, IgE). No IgG2a were seen when the SGE-2 were administered alone or with alum or ricin. It is therefore suggested that first responses would be Th1 and the second ones Th2, although no IgE is seen in the latter responses either. The parasites do not require complement to feed; by contrast, they block its activation and skin cellular infiltrates, such as those elicited by IL-8, MCP-1 and C5a, do not affect them, regardless of the presence or not of antitick antibodies.
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PMID:Host immune response evasion strategies in Ornithodoros erraticus and O. moubata and their relationship to the development of an antiargasid vaccine. 934 16

Shiga toxin (Stx) has an A1-B5 subunit structure, and the A subunit is an RNA N-glycosidase that inhibits cellular protein synthesis. We previously reported that in Caco-2 cells Stx induced cytokines and that the RNA N-glycosidase activity was essential for the cytokine induction. It is known that the binding of the Stx-B subunit to its receptor glycolipid, Gb3, mediates an A subunit-independent signal in some types of cells, but the involvement of this signal in the cytokine induction is unclear. In this study, we investigated whether RNA N-glycosidase itself induces cytokines. IL-8 production was enhanced by Stx, ricin, and modeccin, three toxins that inhibit protein synthesis through an identical RNA N-glycosidase activity, but not by two other types of protein synthesis inhibitors, diphtheria toxin and cycloheximide. The RNA N-glycosidase-type toxins showed a similar induction pattern of cytokine mRNAs. Brefeldin A, a Golgi apparatus inhibitor, completely suppressed the cytokine induction by the toxins. Analysis by using inhibitors of toxin binding and also Stx-B subunit showed that the cytokine-inducing activity was independent of Gb3-mediated signaling. These results indicate that RNA N-glycosidase itself induces the cytokine production and that intracellular transport of toxins through the Golgi apparatus is essential for the activity.
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PMID:Induction of cytokines by toxins that have an identical RNA N-glycosidase activity: Shiga toxin, ricin, and modeccin. 1502 44

Polymorphonuclear cell (PMN) infiltration is a hallmark of ricin-induced mucosal inflammation, yet the cellular processes involved in initiating this reaction remain undefined. In this study we report that ricin stimulates the human monocyte/macrophages cell line 28SC to secrete IL-8, a potent PMN chemoattractant. IL-8 release in response to ricin was both dose- and time-dependent. 28SC cells did not secrete IL-8 when exposed to formaldehyde-inactivated holotoxin or ricin B subunit. Furthermore, IL-8 induction could be blocked by brefeldin A, which inhibits ricin translocation into the cytosol. As predicted from the literature, we observed elevated levels of p38 mitogen activated protein kinase (MAPK), a post-transcriptional regulator of IL-8, in 28SC cells as early as 3h after ricin exposure. Treatment of 28SC cells with the pyridylimidizole analogue SB203580, a known inhibitor of p38 MAPK, suppressed ricin-mediated IL-8 release. We conclude that ricin stimulates human monocyte/macrophages to produce IL-8 by activation of the p38 MAPK pathway, raising the possibility that p38 MAPK inhibitors may potentially serve as therapeutic agents to suppress mucosal inflammation associated with ricin intoxication.
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PMID:Ricin induces IL-8 secretion from human monocyte/macrophages by activating the p38 MAP kinase pathway. 1643 99

Translational inhibitors such as the trichothecene mycotoxin deoxynivalenol (DON) and ribosomal inhibitory proteins (RIPs) induce mitogen-activated protein kinase (MAPK)-driven chemokine and cytokine production by a mechanism known as the ribotoxic stress response (RSR). Double-stranded RNA-activated protein kinase (PKR) associates with the ribosome making it uniquely positioned to sense 28S ribosomal RNA damage and initiate the RSR. We have previously shown that PKR mediates DON-induced MAPK phosphorylation in macrophages and monocytes. The purpose of this study was to test the hypothesis that PKR is essential for induction of interleukin (IL)-8 expression in monocytes by DON and two prototypical RIPs, ricin, and Shiga toxin 1 (Stx1). Preincubation of human monocytic U937 cells with the PKR inhibitors C16 and 2-aminopurine (2-AP) blocked DON-induced expression of IL-8 protein and mRNA. Induction of IL-8 expression was similarly impaired in U937 cells stably transfected with a dominant negative PKR plasmid (UK9M) as compared with cells transfected with control plasmid (UK9C). Nuclear factor-kappa B binding, which has been previously shown to be a requisite for DON-induced IL-8 transcription, was markedly reduced in UK9M cells as compared with UK9C cells. As observed for DON, ricin-, and Stx1-induced IL-8 expression was suppressed by the PKR inhibitors C16 and 2-AP as well as impaired in UK9M cells. Taken together, these data indicate that PKR plays a common role in IL-8 induction by DON and the two RIPs, suggesting that this kinase might be a critical factor in RSR.
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PMID:Double-stranded RNA-activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, Shiga toxin 1, and ricin in monocytes. 1859 99

Hemolytic uremic syndrome (HUS) is the life-threatenig sequela of intestinal infections by Shiga toxin (Stx)-producing Escherichia coli (STEC) in children. Human neutrophils specifically bind Stx through TLR4, the receptor of LPS. The binding could be considered protective (Stx sequestration) or harmful (toxin delivery to target organs). The amount of Stx on neutrophils is in equilibrium with the amount of Stx present in the gut, and it is also related to renal and neurologic symptoms. The TLR4-mediated interaction of LPS with innate immune cells is hampered by the well-known antibiotic polymyxin B. In this study, we show that the same antibiotic impairs the binding of Stx to neutrophils, also blocking their functional effects (release of CXCL8, formation of neutrophil/platelet aggregates) involved in HUS pathogenesis. Controls for contaminating LPS in Stx-induced neutrophil responses inhibited by polymyxin B were performed. Stx interact with human neutrophils through their A chain, since these leukocytes do not express globotriaosylceramide, the specific receptor for Stx B chains. Consistently, polymyxin B blocked the enzymatic activity of Stx1, Stx2, Stx1 A chain, and the analogous plant protein gelonin, whereas the antibiotic did not show any protective effect on Stx-induced cytotoxicity in globotriaosylceramide-expressing Raji cells. Antibiotic administration is not recommended in human STEC infections during the prodromal intestinal phase, and the toxicity of polymyxin B could further discourage its therapeutic use. However, nontoxic, nonbactericidal polymyxin derivatives have been developed and might be used in animal models of STEC infection to study their efficacy in preventing the onset of HUS during the systemic blood phase of Stx.
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PMID:The Antibiotic Polymyxin B Impairs the Interactions between Shiga Toxins and Human Neutrophils. 2669 72