Polymyxin B suppresses the endotoxin inhibition of concanavalin a-mediated erythrocyte agglutination

Warren, Janet I.

doi:10.1128/iai.35.2.594-599.1982

Cited by 17 publications

(7 citation statements)

References 20 publications

(20 reference statements)

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“…To determine the specificity of LPS action on IL-6 production, VSMCs were treated with a specific LPS inhibitor, polymyxin B , which has been reported to form a stable complex with the lipid A moiety of LPS [ 21 ]. Polymyxin B dose-dependently abolished the LPS-induced IL-6 production, but not the pam3CSK4-induced IL-6 production ( Figure 1 B,C).…”

Section: Resultsmentioning

confidence: 99%

TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function

Lee

Tsai

et al. 2016

IJMS

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Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4-driven VSMC migration but not IL-6 production. Importantly, the serum level of IL-6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1-mediated actin cytoskeleton to promote VSMC migration.

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Section: Resultsmentioning

confidence: 99%

TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function

Lee

Tsai

et al. 2016

IJMS

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“…It was found that 160 U of polymyxin B per ml (20 ,ug/ml) neutralized 0.5 to 1 jig of LPS per ml, but this was not sufficient to abolish the effect of higher LPS concentrations. When expressed on a weight basis, the requirement of polymyxin B for neutralizing LPS in our model appeared greater than was reported by other investigators, who used a different experimental system (9,33). This might be due to the fact that polymyxin B also has a great affinity for phospholipids (5) and interacts with enzymes that contain a phospholipid-binding domain (26).…”

Section: Discussionmentioning

confidence: 63%

“…Effect of polymyxin B and E (colimycin) on LPS-induced fibrinolytic inhibition. Polymyxin B has been shown to block several LPS effects (5,18,23,27,30,33), probably by binding to the lipid A moiety (24). Therefore, we tested the ability of this antibiotic at various concentrations (8 to 400 U/ml, i.e., 1 to 50 ,ug/ml) to suppress the urokinase fibrinolytic inhibition induced by 1 ,ug of LPS per ml (Fig.…”

Section: Methodsmentioning

confidence: 99%

Effect of polymyxin B and colimycin on induction of plasminogen antiactivator by lipopolysaccharide in human endothelial cell culture

Dubor¹,

Dosne²,

Chedid³

1986

Infect Immun

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The effect of lipopolysaccharide (LPS) on the production of fibrinolytic inhibitor by human endothelial cells was determined because results of previous experiments have shown us that it is possible to stimulate this synthesis with muramyl dipeptide. Treatment of these cells with LPS resulted in a marked enhancement of fibrinolytic inhibitor, as estimated in a urokinase-induced fibrinolysis assay. A dose-response curve was obtained for LPS concentrations ranging from 10 to 1,000 ng/ml, thus demonstrating the great sensitivity of these cells. This inhibitor did not reduce plasmin activity and formed complexes with highand low-molecularweight urokinase as visualized by fibrin enzymography on sodium dodecyl sulfate-polyacrylamide electrophoretic gels. The molecular weight of this inhibitor was estimated to be 54 to 58 kilodaltons. These findings led us to conclude that LPS stimulates formation of a plasminogen antiactivator. This LPS effect could be suppressed by polymyxin B and colimycin. The stimulatory effect of muramyl dipeptide required doses which were at least 1,000 times greater than those of LPS and was not decreased by polymyxin B. These results show the possibility of independent modulation of plasminogen antiactivator production at the endothelial level, which could be important in endotoxemia. Under these conditions colimycin might have an additional advantage for clinical use because of its ability to prevent fibrinolytic inhibition.

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“…No significant effect of IL-17 was observed in cultures from IL-17RA KO mice ( Figure 3(d) ; compare with Figure 1(a) ). Also, polymyxin, an effective neutralizer for endotoxin [ 43 ], did not change the effectiveness of IL-17A 1–10 ng/mL, when present in excess relative to the expected level of residual endotoxin [ 44 ]. Together, these observations rule out the possibility of the effect of IL-17A 1 ng/mL being accounted for by carryover of LPS, rather than by the cytokine itself, a possibility raised by some studies [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Blockage of Eosinopoiesis by IL‐17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation

Xavier−Elsas

Luca

Queto

et al. 2015

Mediators of Inflammation

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Interleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity, potently stimulates bone-marrow neutrophil production. To explore IL-17A effects on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking inducible nitric oxide synthase (iNOS−/−), CD95 (lpr), IL-17RA, or IL-4, with IL-5, alone or associated with IL-17A. Synergisms between IL-17A-activated, NO-dependent, and NO-independent mechanisms and antagonisms between IL-17A and proallergic factors were further examined. While IL-17A (0.1–10 ng/mL) had no IL-5-independent effect on eosinopoiesis, it dose-dependently suppressed IL-5-induced eosinophil differentiation, by acting during the initial 24 hours. Its effectiveness was abolished by caspase inhibitor, zVAD-fmk. The effect of IL-17A (0.1–1 ng/mL) was sensitive to the iNOS-selective inhibitor aminoguanidine and undetectable in iNOS−/− bone-marrow. By contrast, a higher IL-17A concentration (10 ng/mL) retained significant suppressive effect in both conditions, unmasking a high-end iNOS-independent mechanism. Lower IL-17A concentrations synergized with NO donor nitroprusside. Eosinopoiesis suppression by IL-17A was (a) undetectable in bone-marrow lacking IL-17RA or CD95 and (b) actively prevented by LTD4, LTC4, IL-13, and eotaxin. Sensitivity to IL-17A was increased in bone-marrow lacking IL-4; adding IL-4 to the cultures restored IL-5 responses to control levels. Therefore, effects of both IL-17A and proallergic factors are transduced by the iNOS-CD95 pathway in isolated bone-marrow.

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Polymyxin B suppresses the endotoxin inhibition of concanavalin a-mediated erythrocyte agglutination

Cited by 17 publications

References 20 publications

TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function

TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function

Effect of polymyxin B and colimycin on induction of plasminogen antiactivator by lipopolysaccharide in human endothelial cell culture

Blockage of Eosinopoiesis by IL‐17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation

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