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)

Recent work has established that bacterial endotoxin (LPS) binds to the plasma protein LPS-binding protein (LBP) forming high affinity complexes (LPS-LBP), that LBP is an opsonin for LPS-bearing particles, and that LPS-LBP complexes are potent agonists for monocytic cells (MO). mAb to the MO plasma membrane protein, CD14, inhibit LBP-dependent binding of LPS to MO, and LPS-LBP-dependent stimulation of cytokine release from MO. These data suggest that CD14 functions as a membrane receptor for LPS but do not demonstrate a direct association of LPS with CD14. Calcitriol was used to induce a high level of CD14 expression in the human monocyte-like cell line THP-1, resulting in enhanced responses of these cells to LPS-LBP complexes manifested by enhanced binding of LPS and a decrease in the amount of LPS needed to induce IL-8 release. An Re595 LPS derivative containing a radioiodinated, photoreactive, phenyl azide (125I-ASD-LPS) was used in cross-linking experiments to identify membrane proteins in calcitriol-treated THP-1 cells that interact with LPS. 125I-ASD-LPS was added to calcitriol-induced THP-1 cells in the presence or absence of LBP, the mixture photolyzed, and the resultant radioiodinated proteins analyzed by SDS-PAGE and autoradiography. We observed strong cross-linking of 125I-ASD-LPS to a 55-kDa membrane protein when LBP was present, but failed to observe radiolabeling of any other proteins with apparent molecular masses distinct from CD14. The cross-linked product was identified as CD14 by immunoprecipitation with anti-human CD14 mAb. Studies with human CD14 expressing transfectants of the murine B cell line 70Z/3 also revealed LBP-dependent cross-linking of 125I-ASD-LPS to CD14. These data document binding of LPS to a specific membrane protein that serves as an LPS receptor.
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PMID:Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. 768 Oct 85

A critical feature of sepsis-induced adult respiratory distress syndrome (ARDS) is the release of cytokines (such as interleukin [IL]-6, IL-8, and tumor necrosis factor [TNF]) from endotoxin (lipopolysaccharide [LPS])-activated alveolar macrophages (AM). Nuclear factor kappa B (NF-kappaB) is activated in AM from patients with ARDS, and it is essential for the transcription of many cytokine genes. In these studies, we evaluated the regulation of LPS-induced cytokine release and the activation of NF-kappaB in human AM. We found that the activation of NF-kappaB and the release of IL-6, IL-8, and TNF from AM exposed to LPS was protein kinase C-independent and tyrosine kinase- and phosphatidylcholine-specific phospholipase C-dependent. We also found that LPS-induced activation of NF-kappaB was enhanced in AM cultured in serum or in the presence of LPS-binding protein, simulating conditions in the lung that are present in ARDS. In addition, LPS triggered the activation of several different NF-kappaB complexes in AM, and different forms of NF-kappaB bound to the IL-6, IL-8, and TNF promoter sequences. These observations suggest that physiologic abnormalities present in the lungs of patients with ARDS facilitate the activation of NF-kappaB and local release of cytokines.
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PMID:Lipopolysaccharide-induced NF-kappaB activation and cytokine release in human alveolar macrophages is PKC-independent and TK- and PC-PLC-dependent. 949 Jun 56

In an earlier study in Indonesia we reported on adverse reactions to diethylcarbamazine (DEC) in brugian filariasis patients identified as microfilaraemics (n = 26), endemic normals (n = 11) and elephantiasis patients (n = 17). To assess the link between adverse reactions and cytokines we have now analysed an array of inflammatory mediators in plasma samples collected during the same study. Pre-treatment levels of interleukin (IL)-6 and soluble tumour necrosis factor receptor 75 (sTNF-R75) were higher in elephantiasis patients compared to microfilaraemics and endemic normals, indicating the presence of an ongoing inflammation in patients with chronic disease. After initiation of treatment, the levels of IL-6 and LPS-binding protein (LBP) were consistently and significantly higher in microfilaraemics who suffered most from adverse reactions compared with endemic normals and elephantiasis patients. In microfilaraemics the levels of sTNF-R75 increased after treatment to reach levels recorded in elephantiasis patients. IL-6 increased early, concurrent with the development of adverse reactions and peaked by 24 h post treatment. The levels of LBP and sTNF-R75 in microfilaraemics also increased to peak, later than IL-6, at 32 h post DEC therapy. Although changes were recorded in IL-8 and IL-10 levels in some individuals, no significant differences were found between the 3 clinical groups. These results demonstrate that intake of DEC leads to an increase in a selected number of inflammatory mediators in the group of filarial patients who suffer most from adverse systemic reactions.
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PMID:Inflammatory cytokines following diethylcarbamazine (DEC) treatment of different clinical groups in lymphatic filariasis. 1071 62

We have recently shown that highly purified lipoteichoic acid (LTA) represents a major immunostimulatory principle of Staphylococcus aureus. In order to test whether this translates to other bacterial species, we extracted and purified LTA from 12 laboratory-grown species. All LTA induced the release of TNF-alpha, IL-1beta, IL-6 and IL-10 in human whole blood. Soluble CD14 (sCD14) inhibited monokine induction by LTA but failed to confer LTA responsiveness for IL-6 and IL-8 release of human umbilical vein endothelial cells (HUVEC). In a competitive LPS-binding protein (LBP) binding assay, the IC(50) of the tested LTA preparations was up to 3,230-fold higher than for LPS. LBP enhanced TNF-alpha release of human peripheral blood mononuclear cells (PBMC) upon LPS but not LTA stimulation. These data demonstrate a differential role for the serum proteins LBP and sCD14 in the recognition of LPS and LTA. Different efficacies of various anti-CD14 antibodies against LPS vs. LTA-induced cytokine release suggest that the recognition sites of CD14 for LPS and LTA are distinct with a partial overlap. While the maximal achievable monokine release in response to LTA was comparable to LPS, all LTA induced significantly less IL-12 and IFN-gamma. IL-12 substitution increased LTA-inducible IFN-gamma release up to 180-fold, suggesting a critical role of poor LTA-inducible IL-12 for IFN-gamma formation. Pretreatment with IFN-gamma rendered galactosamine-sensitized mice sensitive to challenge with LTA. In conclusion, LTA compared to LPS, are weak inducers of IL-12 and subsequent IFN-gamma formation which might explain their lower toxicity in vivo.
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PMID:Cytokine induction by purified lipoteichoic acids from various bacterial species--role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-gamma release. 1182 71

Activated monocytes and macrophages have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation can be documented by measurement of neopterin, adhesion cell molecules, and certain proinflammatory cytokines and chemokines. We first became interested in the role of monocytes and monocyte-derived cytokines in ALD in relation to altered zinc metabolism that occurs regularly in ALD. Patients with ALD have hypozincemia, which responds poorly to oral zinc supplementation. We have shown that in ALD monocytes make a low-molecular-weight substance that, when injected into rabbits, causes prominent hypozincemia. Subsequently, multiple cytokines [especially tumor necrosis factor (TNF) and interleukin (IL)-8] have been shown to be overproduced by monocytes in ALD. We initially showed that monocytes in ALD spontaneously produce TNF and overproduce TNF in response to a lipopolysaccharide (LPS) stimulus, and this could be attenuated by antioxidants in vitro and in vivo. Alterations in the endotoxin-binding protein LPS-binding protein, in CD14, and in the endotoxin receptor Toll-like receptor 4 all may play roles in enhanced proinflammatory cytokine signaling in ALD. Moreover, several groups have documented increased TNF receptor density in monocytes in ALD. Inadequate negative regulation of TNF occurs at multiple levels in ALD. This includes decreased monocyte production of the important antiinflammatory cytokine IL-10 and blunted response to the antiinflammatory properties of adenosine. Finally, generation of reactive oxygen species (which occurs during alcohol metabolism) and products of lipid peroxidation induce production of cytokines, such as TNF and IL-8. In conclusion, there are multiple overlapping potential mechanisms for enhanced proinflammatory cytokine production by monocytes in ALD. We postulate that activation of monocytes and macrophages with subsequent proinflammatory cytokine production plays an important role in certain metabolic complications of ALD and is a component of the liver injury of ALD.
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PMID:Monocyte activation in alcoholic liver disease. 1206 38

Lipopolysaccharide (LPS) as a major component of the outer membrane of gram-negative bacteria stimulates various cells to initiate a signalling cascade which ultimately leads to cell activation and expression of immunoregulatory or inflammatory cytokines. The human respiratory epithelium is an important environmental interface, but differences in LPS-induced cell activation between bronchial and alveolar epithelial cells have not yet been investigated in detail. First, the expression of Toll-like receptors (TLRs), as pattern-recognition receptors, was investigated for the bronchial epithelial cells and type II-like pneumocytes, demonstrating that they fulfil the prerequisites for LPS signalling. Thereafter, the effects of LPS, soluble CD14 (sCD14) and LPS-binding protein (LBP) on the release of interleukin-6 (IL-6) and IL-8 were studied. In the presence of LPS, sCD14 induced a significant and concentration-dependent cytokine release in type II-like pneumocytes, whereas the response of bronchial epithelial cells to sCD14 stimulation was low, implicating sCD14-independent activation mechanisms. Furthermore, LBP revealed inhibitory effects on the activation of alveolar epithelial cells, which may represent a novel local defence mechanism during gram-negative infection. We conclude that distinct pathways exist for LPS-induced activation of bronchial and alveolar epithelial cells.
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PMID:Differences in LPS-induced activation of bronchial epithelial cells (BEAS-2B) and type II-like pneumocytes (A-549). 1219 31

Lipoarabinomannans (LAMs) are glycolipids from the mycobacterial cell wall that exhibit various biological activities, including proinflammatory and anti-inflammatory responses. However, little is known about the properties of lipomannans (LMs), considered to be precursors of LAMs. In this study, we provide evidence that LMs purified from Mycobacterium chelonae and a clinical strain of Mycobacterium kansasii stimulated mRNA expression and secretion of TNF-alpha and IL-8 from human macrophage-like differentiated THP-1 cells. In contrast to LMs, LAMs were not able to induce a significant cytokine-inducing effect. The mechanism of activation by LMs was investigated using various Abs raised against surface receptors for multiple bacterial products. The presence of anti-CD14 or anti-Toll-like receptor 2 (TLR2) Abs profoundly affected production of TNF-alpha and IL-8, suggesting that both CD14 and TLR2 participate in the LM-mediated activation process. Furthermore, stimulation of cells was dependent on the presence of the LPS-binding protein, a plasma protein that transfers glycolipids to CD14. Chemical degradation of the arabinan domain of mannose-capped LAM from M. kansasii, which presented no cytokine-eliciting effect, restored the cytokine-inducing activity at a level similar to those of LMs. These results support the hypothesis that the presence of an arabinan in LAMs prevents the interaction of these glycolipids with TLR2/CD14 receptors. In addition, we found that phosphatidylinositol dimannosides isolated from M. kansasii did not induce cytokine secretion. This study suggests that LMs isolated from different mycobacterial species participate in the immunomodulation of the infected host and that the D-mannan core of this glycolipid is essential for this function.
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PMID:Lipomannans, but not lipoarabinomannans, purified from Mycobacterium chelonae and Mycobacterium kansasii induce TNF-alpha and IL-8 secretion by a CD14-toll-like receptor 2-dependent mechanism. 1290 6

The objective of the current study was to evaluate the dynamics of infection and the immunological response to varying numbers of Escherichia coli injected into the mammary glands of primiparous cows during the periparturient period. Primiparous cows have been shown to be more resistant to intramammary E. coli challenge, and an increase of the inoculum dose by 2 log10 units induced a more rapid clinical response and clearance of the organisms. Recognition of lipopolysaccharide (LPS) is a key event in the innate immunity response to gram-negative infection and is mediated by the accessory molecules CD14 and LPS-binding protein (LBP). Primiparous cows were inoculated with 1 x 10(4) (Group A; n=8) or 1 x 10(6) (Group B; n=8) cfu E. coli P4:O32 in their 2 left quarters during the periparturient period. Clinical examination and analysis of blood and milk parameters, including IL-8, complement fragment 5a (C5a), LBP, and soluble CD14 (sCD14), were performed from d -4 to d +3 relative to infection. Primiparous cows in Group B initiated a more rapid clinical response following intramammary infection (IMI), resulting in typical clinical signs and changes in blood and milk parameters approximately 3 h earlier compared with primiparous cows in Group A. Based on average milk production in the noninfected quarters on d +2 postinoculation, all heifers reacted as moderate responders. Distinct differences in the kinetic patterns of rectal temperature, somatic cell count (SCC), IL-8, C5a, LBP, and sCD14 were observed between both groups during the early phase of inflammation. Both C5a and IL-8 increased before cellular influx into the infected glands, followed by increases in sCD14 and LBP. In conclusion, primiparous cows are able to clear an intramammary E. coli infection efficiently. Moreover, increasing the inoculum dose induces a more rapid inflammatory reaction, mainly because of early activation of the innate host immune response.
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PMID:Increase of Escherichia coli inoculum doses induces faster innate immune response in primiparous cows. 1554 75

Heparin is one of the most effective drugs for preventing and treating thromboembolic complications in surgical patients. Recent evidence suggests that heparin enhances the proinflammatory responses of human peripheral blood monocytes to Gram-negative endotoxin (LPS). We have identified LPS-binding protein (LBP) as a novel heparin-binding plasma protein. The affinity of LPB to heparin was KD = 55 +/- 8 nM, as measured by surface plasmon resonance. Using a fluorescence-based assay, we showed that clinically used heparin preparations significantly enhance the ability of LBP to catalytically disaggregate and transfer LPS to CD14, the LPS receptor. The presence of clinically relevant heparin concentrations in human whole blood increased LPS-induced production of the proinflammatory cytokine IL-8. Fondaparinux, which is identical with the antithrombin III-binding pentasaccharide in heparin, did not bind to LBP or alter LBP function. Thus, this novel anticoagulant drug is a potential candidate for safe administration to patients who have endotoxemia and require anticoagulation.
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PMID:Heparin binds to lipopolysaccharide (LPS)-binding protein, facilitates the transfer of LPS to CD14, and enhances LPS-induced activation of peripheral blood monocytes. 1569 63

Oral treponemes are well-known as causative agents of periodontal diseases; however, the details have not been fully clarified. Here, we examined the effects of Treponema medium glycoconjugate on the activation of human gingival fibroblasts using phenol-water extracts from Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum subsp. nucleatum, and Actinobacillus actinomycetemcomitans. The phenol-water extracts activated human gingival fibroblasts to mediate IL-8 production, as well as IL-8 mRNA expression, phosphorylation of p38 mitogen-activated protein kinase, and expression of intercellular adhesion molecule-1. T. medium glycoconjugate exhibited no activation of human gingival fibroblasts, while phenol-water extract-induced activation of human gingival fibroblasts was clearly inhibited by T. medium glycoconjugate. Furthermore, binding of biotinylated phenol-water extracts to CD14 in the presence of LPS-binding protein was blocked with T. medium glycoconjugate. These results suggest that T. medium glycoconjugate has an inhibitory effect on host cell activation by periodontopathic bacteria caused by binding to CD14- and LPS-binding protein.
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PMID:Treponema medium glycoconjugate inhibits activation of human gingival fibroblasts stimulated with phenol-water extracts of periodontopathic bacteria. 1584 Jul 83


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