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)

In vitro-studies have shown that phospholipid hydrolysis of low density lipoproteins (LDL) by bee venom or porcine pancreatic phospholipase A2 (PLA2) leads to an increased uptake of these lipoproteins by macrophages transforming them into foam cells. Recently, a secretory phospholipase A2, group II, was detected in human atherosclerotic plaques. In order to investigate the role of this enzyme in the pathogenesis of atherosclerosis, a structurally identical human secretory PLA2 was purified from the medium of HepG2 cells stimulated with interleukin-6 and tumor necrosis factor-alpha. The activity of the purified enzyme towards the phospholipids of native and modified low density lipoproteins was compared with the activity towards Escherichia coli-membranes and other phospholipid substrates. Compared to E. coli-membranes, native LDL proved to be a poor substrate for group II PLA2. After mild oxidation induced by copper ions or by 2,2-azobis(2-amidinopropane) (AAPH), the susceptibility of LDL to phospholipid hydrolysis was found to be increased by 25 and 23%, respectively, whereas extensive copper-mediated oxidation caused a decreased hydrolysis. Aging of LDL at 6 degrees C for weeks or at 37 degrees C for hours resulted in an increase in PLA2-catalyzed phospholipid hydrolysis of up to 26-fold. LDL protected from oxidation by probucol during aging showed a lesser increase in susceptibility to phospholipid hydrolysis. Our results suggest that PLA2, group II, can increase the atherogenicity of LDL by its ability to hydrolyze the phospholipids of these lipoproteins, especially after modifications that are likely to occur in vivo.
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PMID:Minimal oxidation and storage of low density lipoproteins result in an increased susceptibility to phospholipid hydrolysis by phospholipase A2. 924 62

In this study, we determined the serum levels of mannan-binding lectin (MBL) in patients with suspected or documented infection to characterize the possible role of MBL in the susceptibility to infection. We also investigated the kinetics of MBL during the infection and correlated the concentrations of MBL with those of acute-phase reactants C-reactive protein (CRP) and group II phospholipase A2 (PLA2-II) and cytokines interleukin-1(IL-1). interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). The frequency of MBL deficiency in the patients with signs of infection did not differ from that of controls. In four patients with MBL deficiency, the infections were caused by common pathogens and the outcome was normal. The mean MBL concentration in the patients with signs of infection was significantly higher than in the healthy controls (9.88 and 4.48 mg/l, respectively; p < 0.05). The highest mean MBL concentration was observed in patients with clinically or microbiologically documented bacterial infection. During follow-up, the MBL concentration altered individually in different patients, but no particular change in pattern in the MBL concentration could be demonstrated in any patient group. Of the acute-phase reactants in the circulation, only CRP and IL-1 showed a weak, albeit significant, negative correlation with the concentration of MBL. In conclusion, the deficiency of MBL was not shown to be an independent risk factor for infection in the adult population studied. The concentration of MBL did not follow the change in pattern of other acute-phase reactants and cytokines during the acute phase response. Therefore, measurement of the MBL concentration as an acute-phase reactant is not useful in the diagnosis or follow-up of infection. On the other hand, the deficiency of MBL can be detected reliably by serological methods even during an infection.
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PMID:Serum mannan-binding lectin (MBL) in patients with infection: clinical and laboratory correlates. 929

Severe acute pancreatitis has many similarities to sepsis syndrome and septic shock. The haemodynamic features of cardiovascular instability, reduced ejection fraction and decreased systemic vascular resistance are indistinguishable in each of these conditions. In addition there are many striking similarities in the cytokine and inflammatory mediator profiles, suggesting that the haemodynamic abnormalities may result from the same pathogenic mechanisms, albeit as a result of different inflammatory stimuli. Although septic complications of severe acute pancreatitis do arise these are usually late features and in the early phase of a severe attack there is sterile pancreatic necrosis. Evidence suggests that the important cytokines in the development of complications and multiple organ failure in severe acute pancreatitis are tumour necrosis factor-alpha, interleukin-1, interleukin-6 and interleukin-8. In addition, endotoxin and other important inflammatory mediators including platelet activating factor and phospholipase A2 are implicated in the development of complications in both severe acute pancreatitis and sepsis. Patients with severe acute pancreatitis are not an entirely homogeneous group but in terms of pathogenesis and complications of their disease they have much more in common with each other than the patients who are collected under the unifying diagnosis of 'sepsis'. The similar clinical and biochemical features between severe acute pancreatitis and sepsis make the former an excellent model for studying the pathogenesis of the sepsis syndrome.
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PMID:Acute pancreatitis as a model of sepsis. 951 Oct 87

Secretory nonpancreatic group IIA phospholipase A2 (sPLA2), a lipolytic enzyme found in plasma, is thought to play an important role in inflammation. In patients with sepsis, a strong positive correlation is observed between the plasma level of sPLA2 and poor clinical outcome in sepsis. We have thus asked whether sPLA2 could play a role in enabling responses of cells to bacterial lipopolysaccharide (LPS), a key contributor to sepsis. In the presence of sPLA2, cellular responses to LPS were significantly increased. This was demonstrated in assays of LPS-stimulated interleukin-6 (IL-6) production in whole blood and binding of freshly isolated human polymorphonuclear neutrophils (PMN) to fibrinogen-coated surfaces. We further found that sPLA2 enhanced binding of labeled LPS to PMN, and that the sPLA2-mediated cell responses to LPS were all blocked by monoclonal antibodies directed against membrane CD14. Two properties ofsPLA2 may contribute to its activity to mediate responses to LPS. sPLA2 appears to bind LPS because pre-exposure of sPLA2 to LPS led to a dose-dependent increase in its ability to hydrolyze phospholid substrate, and incubation of sPLA2 with BODIPY-LPS micelles resulted in enhanced fluorescence, presumably from the disaggregation of the LPS aggregates. Additional studies demonstrated that the esterolytic function of sPLA2 is also needed both for the disaggregation of LPS and CD14-dependent cell stimulation. The precise mechanisms by which LPS-binding and esterolytic activity contribute to sPLA2 activity are not clear but our data strongly suggest that these activities result in interaction of LPS with CD14 and subsequent cell activation.
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PMID:Enhancement of leukocyte response to lipopolysaccharide by secretory group IIA phospholipase A2. 1038 Aug 95

The purpose of this study was to examine whether mRNA of interleukin-A2, interleukin-6, phospholipase A2, and nitric oxide synthase was expressed in the nerve root and dorsal root ganglion of an animal model in which exposure to the nucleus pulposus induced mechanical hyperalgesia, a pain-related behavior. Autologous nucleus pulposus obtained from coccygeal discs was relocated on the L4 and L5 lumbar nerve roots after partial laminectomy. The reflex response to noxious mechanical stimuli to the hindpaw was measured preoperatively and to 4 weeks postoperatively. With a reverse transcription-polymerase chain reaction technique, expression of interleukin-1beta, interleukin-6, phospholipase A2, and inducible nitric oxide synthase genes in the nerve root and dorsal root ganglion was observed at 1, 2, and 4 weeks postoperatively. Mechanical hyperalgesia was observed from 3 days to 2 weeks postoperatively. The expression of interleukin-1beta, phospholipase A2, and inducible nitric oxide synthase mRNAs increased after only 1 week. This increase was related to mechanical hyperalgesia. Expression of interleukin-6 was detected in the neural tissue over time. It is possible that interleukin-1beta, phospholipase A2, and inducible nitric oxide in the nerve root or dorsal root ganglion, or in both, produce sciatic pain in the early stage of herniation of the lumbar disc.
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PMID:mRNA expression of interleukins, phospholipase A2, and nitric oxide synthase in the nerve root and dorsal root ganglion induced by autologous nucleus pulposus in the rat. 1063 62

In a previous study, we have demonstrated that sodium arsenite (arsenite) as chemical stress stimulates heat shock protein 27 (HSP27) induction and arachidonic acid release in osteoblast-like MC3T3-E1 cells, and that the response of HSP27 induction is coupled with metabolic activity of the arachidonic acid cascade. In the present study, we examined the effect of exposure to arsenite on the synthesis of interleukin-6 (IL-6) in these cells. Arsenite induced the synthesis of IL-6 after 6 h from the stimulation up to 48 h. The effect of arsenite on IL-6 synthesis was dose-dependent in the range between 10 and 500 microM. The arsenite-induced IL-6 synthesis was enhanced by the pretreatment with indomethacin, an inhibitor of cyclooxygenase. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly amplified the arsenite-induced IL-6 synthesis. Melittin, an activator of phospholipase A2, which by itself hardly affected the levels of IL-6, markedly enhanced the arsenite-induced IL-6 synthesis. These results strongly suggest that chemical stress induces IL-6 synthesis in osteoblasts, and that the IL-6 synthesis is coupled to the arachidonic acid cascade as well as the HSP27 induction by arsenite.
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PMID:Involvement of arachidonic acid in chemical stress-induced interleukin-6 synthesis in osteoblast-like cells: comparison with heat shock protein 27 induction. 1084 Oct 42

Antiflammins are synthetic peptides derived from the region of highest local similarity between uteroglobulin and lipocortin. These peptides have shown anti-inflammatory activity on carrageenan-induced rat footpad edema. They are potent inhibitors for phospholipase A2 activation both in vitro and in vivo. Previously, we have demonstrated the effectiveness of topical antiflammins in suppressing acute ocular inflammation and allergic response in rodent endotoxin-induced uveitis and murine allergic conjunctivitis. The mechanisms by which antiflammins protect against inflammation and allergy in these ocular models may involve inhibition of phospholipase A2 and inducible nitric oxide synthase (iNOS) as well as the production of proinflammatory cytokine, interleukin-6.
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PMID:Therapeutic applications of antiflammin peptides in experimental ocular inflammation. 1119 52

To assess the potential role of interleukin-6 (IL-6) in the pathogenesis of dengue virus infection, levels of this cytokine were measured in children with dengue virus infection on admission to the hospital. As presumed surrogate markers of IL-6, C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured. Three groups were studied: 33 apparently healthy children as negative controls, 11 children with bacterial infections as positive controls, and 186 children with serologically documented dengue virus infection. One-hundred and fifteen patients had dengue fever (DF) and 71 had dengue hemorrhagic fever (DHF). Compared with healthy controls, dengue shock syndrome (DSS) patients had significantly higher levels of IL-6 on admission (P < 0.05), comparable with those in positive controls. Dengue patients with shock had significantly higher levels of IL-6 than normotensive patients (P < 0.001) and higher levels of IL-6 were associated with a higher incidence of ascites. C-reactive protein concentrations in dengue patients and in healthy children were not different, but lower than in children with bacterial infections (P = 0.008). Secretory phospholipase A2 levels were higher in dengue patients than in apparently healthy children (P < or = 0.05) and similar to those in children with bacterial infection. Dengue shock syndrome patients had significantly higher sPLA2 concentrations than normotensive patients (P = 0.02). These data indicate that IL-6 and sPLA2 may have a pathogenetic role only in the most severe forms of dengue virus infection.
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PMID:Inflammatory mediators in dengue virus infection in children: interleukin-6 and its relation to C-reactive protein and secretory phospholipase A2. 1150 11

Inflammation of the synovial membrane in rheumatoid arthritis is mediated by specialized cells necessary for immune response. The most prominent features are the accumulation of mononuclear phagocytes, lymphocytes and leukocytes in the proliferating tissue. Pro-inflammatory and proliferative signals are transmitted to the bone marrow and to the synovial membrane. The result is a monoclonal stimulation of specific cell lines, and synovial proliferation in the inflamed joint. Angiogenesis, synovial hypertrophy, and increased perfusion facilitate the accumulation of inflammatory cells. Components of the autoimmune reaction are described in the international system of classification, the CD-System (cluster of differentiation). Pro-inflammatory signals are mediated by metabolites of arachidonic acid. Prostaglandins, leukotrienes, lipoxines and hydroxy fatty acids, derived from this PUFA, stimulate the formation and the activity of adhesion molecules (integrines), cytokines (gamma-interferon, interleukin-1, interleukin-6, tumor-necrosis factor), chemokines (interleukine-8, macrophage-chemotactic peptide, RANTES and colony -stimulating factors ((CSF, granulocytes/ monocytes-CSF, Multi-CSF (= IL-3)). Dietary means to mitigate inflammation comprise reduction of arachidonic acid, and increased intake of eicosapentaenoic acid and antioxidants. In the literature 12 randomized, placebo-controlled double-blind studies, fulfilling GCP-criteria, demonstrate a moderate but consistent improvement of clinical findings and laboratory parameters in patients with RA. A dose-response relationship was established up to an daily dose of 2.6 gram fish oil, equivalent to about 1.6 gram EPA. In these experiments EPA was the omega-3 fatty acid responsible for improvement, with distinct effects on inhibition of cytokines formation (IL-1 to IL-6, IL-8, TFN-alpha, GM-CSF), decreased induction of proinflammatory adhesion molecules (selectines, intercellular adhesions molecule-1 (ICAM-1)), and degrading enzymes (e.g. phospholipase A2, cyclooxygenase-2, inducible NO-synthetase). Only one study reports the relevance of the background diet. From this study it became apparent that reduction of dietary arachidonic acid improves the incorporation and the clinical benefit of EPA.
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PMID:Dietary fatty acids and immune reactions in synovial tissue. 1291 34

Studies were conducted to characterize a HeLa cell model by which the roles of the 85-kDa phospholipase A2 (cPLA2) in interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) release could be evaluated. At first, untreated HeLa cells were compared with lipopolysaccharide (LPS)-treated HeLa cells. The latter resulted in cPLA2 overexpression and an increased trend of IL-1 beta and IL-6 release. The indicated doses of 85-kDa cPLA2 antisense oligonucleotide directed against the initiation site were then used to block cPLA2 in LPS-induced HeLa cells. The process led to a dose-dependent decrease in cPLA2 protein with no noticeable change of cPLA2 mRNA. Compared with that of LPS added only, a reduction of IL-1 beta and IL-6 levels in the supernatants of transfected cells following the repression of cPLA2 was observed. These results suggested that 85-kDa cPLA2 may mediate the signalling cascades by which IL-1 beta and IL-6 were released in LPS-induced HeLa cells.
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PMID:The mediating role of cPLA2 in IL-1 beta and IL-6 release in LPS-induced HeLa cells. 1469 53


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