Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.
 ...
PMID:IL-1-like production in adriamycin-induced nephrotic syndrome in the rat. 173 26

In order to further characterize monocyte function in patients with lipoid nephrosis (LN), we studied the production of interleukin-1 (IL-1). In this study we examined the ability of peripheral blood monocytes (PBM) from LN patients to produce this monokine in vitro under the stimulus of bacterial lipopolysaccharide (LPS). The levels of IL-1 were decreased in patients with LN compared with those in normal controls and lower in LN patients with nephrotic syndrome (NS) than in those without NS. In contrast, the values in IgA nephropathy (IgAN) patients with or without NS did not differ from normal subjects. The addition of indomethacin, an inhibitor of prostaglandin synthesis, partially restored this defect. These results suggest that the impaired IL-1 production of LN PBM is probably attributable, at least in part, to increased prostaglandin production and possibly influences the immune status of LN patients.
 ...
PMID:Decreased production of interleukin-1 by monocytes from patients with lipoid nephrosis. 278 18

A study was made of the nature of secondary immuno-deficiency, peculiarities of disordered function of regulatory T-lymphocytes (helpers and suppressors), and their interrelationships in different clinical variants of chronic glomerulonephritis (CGN). Altogether 94 CGN patients were examined, of them 34 were with urinary syndrome and 60 with nephrotic syndrome. With relation to a clinical variant of disease the absolute amount of T-lymphocytes was significantly lowered, the amount and function of B-lymphocytes showed a tendency to an increase. Function of nonspecific Concanavalin A-induced T-suppressors using PHA as a mitogenic indicator (T-T-suppression) was insignificantly raised, and when lipopolysaccharide (T-B-suppression) was used it was considerably suppressed. T-lymphocyte helper activity in CGN patients was on an increase.
 ...
PMID:[Characterization of secondary immune deficiency in patients with chronic glomerulonephritis]. 296 Nov

IL-10, a cross-regulatory cytokine produced by several cell types, including monocytes, is known to stimulate B cell growth and maturation and to inhibit cytokine production. In order to characterize further monocyte function in patients with lipoid nephrosis (LN), the release of IL-10 was measured in supernatants of cultured peripheral blood monocytes (PBM) that were obtained from LN patients and healthy controls. Spontaneous and lipopolysaccharide (LPS)-induced IL-10 release was decreased in patients with LN compared with those in normal controls and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the values in IgA nephropathy (IgAN) patients with or without NS did not differ from normal subjects. There was a negative correlation between IL-10 concentration and the quantity of vascular permeability factor (VPF) released in LN patients. These imply that there is a relative deficit in IL-10 release in active LN, which suggests the possibility that inadequate release of IL-10 may lead to increased VPF activity in active LN patients and the measurements of IL-10 may be of value for monitoring kidney disease. The data provide the first detailed analysis of IL-10 in a group of patients with LN.
 ...
PMID:Decreased release of IL-10 by monocytes from patients with lipoid nephrosis. 853 79

The pathogenesis of minimal-change nephrotic syndrome (MCNS) is obscure. It has been postulated that this glomerular disease may be a systemic disorder of cell-mediated immunity. IL-12 is a heterodimeric cytokine that is produced primarily by antigen-presenting cells and plays a primary role in the induction of cell-mediated immunity. To gain insight into the involvement of this cytokine, in vitro IL-12 levels were assessed in patients with MCNS and IgA nephropathy (IgAN) who were in either a stable or active clinical condition. The levels were compared with values in healthy controls. Significantly increased spontaneous and lipopolysaccharide (LPS)-stimulated release of IL-12 was detected in peripheral blood monocyte (PBM) cultures of MCNS and IgAN patients with the nephrotic syndrome (NS) compared with those of normal controls. Moreover, when individual MCNS patients were followed through their clinical illness, IL-12 levels were increased during the active phase and normalized as the patients went into remission. The amounts of IL-12 are significantly correlated with the levels of vascular permeability factor (VPF) in MCNS patients. This study describes a correlation between in vitro IL-12 release by PBM from two types of nephrotic patients and their disease activity, as well as a correlation with release of VPF by the same cultures. The study contributes to the understanding of this class of diseases and the observations may have a prognostic/diagnostic value.
 ...
PMID:Increased IL-12 release by monocytes in nephrotic patients. 1044 71

Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.
 ...
PMID:Childhood nephrotic syndrome in relapse is associated with down-regulation of monocyte CD14 expression and lipopolysaccharide-induced tumour necrosis factor-alpha production. 1297 63

The pathogenesis of glomerular alterations and proteinuria in corticosteroid-responsive nephrotic syndrome (CRNS) is unknown. As an isoform of plasma hemopexin (Hx) with protease activity may be implicated in this disease, we have studied the inhibition of Hx by ADP and reactivation to its active form by endothelial or mesangial cells in vitro. We hypothesized that these cells might potentially be able to convert the inactivated form of Hx (Hxi) to active Hx (Hxa) in vitro, mediated by cellular ecto-ADPase. Since ecto-ADPase (CD39) is upregulated after stimulation of these cells with lipopolysaccharide (LPS) or certain cytokines, we postulated that this conversion might occur specifically after inflammatory stimulation of these cells. Human endothelial or mesangial cell cultures were incubated overnight with or without LPS (10.0 ng/ml) or TNFalpha (10.0 ng/ml), washed and subsequently incubated with Hxi (1.5 mg/ml) in serum-free conditions (Hxi was prepared by treatment of Hxa with ADP or ADP-beta-S). After 60 min, supernatants were tested for their capacity to alter glomerular extracellular matrix molecules (i.e. ecto-apyrase) in vitro using standard methods, and compared with Hxi that had not been incubated with cells. Supernatants containing Hxa (1.5 mg/ml) served as positive control. The results show significant activity in supernatants with Hxi (prepared using native ADP). However, Hxi inactivated by ADP-beta-S (which is non-hydrolyzable) could not be reactivated after contact with LPS-stimulated or unstimulated cells in vitro. As ecto-ADPase of these cells is upregulated by LPS, we believe that reactivation of Hxi to Hxa is mediated by cellular ecto-ADPase. Although the relevance of this inflammation-mediated activation mechanism of Hx in patients with CRNS requires further experimentation, our preliminary observations suggesting that this mechanism is corticosteroid dependent may support a potential role of Hxa in CRNS.
 ...
PMID:Regulation of plasma hemopexin activity by stimulated endothelial or mesangial cells. 1475 38

Endothelial as well as mesangial cells show enhanced activity of ecto-apyrase following pro-inflammatory stimulation in vitro. Since this ecto-enzyme appears to be able to regulate plasma hemopexin, which latter molecule plays a role in the pathogenesis of corticosteroid responsive nephrotic syndrome, the question was raised whether glucocorticoids are potentially able to downregulate ecto-apyrase activity of these cells. Therefore, cell cultures of endothelial or mesangial were stimulated with or without lipopolysaccharide (10 ng/ml). Parallel cultures were supplemented with prednisolone with or without the glucocorticoid receptor antagonist mifepristone in various concentrations. After 24 h, cytospins were prepared and cytochemically stained for ecto-apyrase activity. mRNA for apyrase of these cells was detected using reverse transcription-polymerase chain reaction (RT-PCR). Apyrase activity of either cells or soluble apyrase (0.16 U/ml buffer) with or without supplementation of prednisolone were biochemically assayed for their phosphatase activity. The results show significantly decreased ecto-apyrase activity of lipopolysaccharide-stimulated cells after treatment with prednisolone as compared to non-prednisolone-treated cells. Preincubation with mifepristone did not inhibit the effect of prednisolone. Identical mRNA signals for apyrase were found in prednisolone and non-prednisolone-treated cells. Interestingly, soluble apyrase also showed a significant decrease of activity following preincubation with prednisolone. It is concluded that prednisolone is able to downregulate ecto-apyrase of stimulated endothelial or mesangial cells, which may potentially inhibit the conversion of hemopexin to its pro-inflammatory isoform. As blocking of the cytosolic glucocorticoid receptor showed no effect upon the prednisolone action, whereas prednisolone is able to affect soluble apyrase per se, it is felt that this particular action of prednisolone may (at least partly) be mediated through a non-genomic pathway.
 ...
PMID:Enhanced ecto-apyrase activity of stimulated endothelial or mesangial cells is downregulated by glucocorticoids in vitro. 1546 78

The actin-based foot processes of kidney podocytes and the interposed slit diaphragm form the final barrier to proteinuria. Mutations affecting several podocyte proteins cause disruption of the filtration barrier and rearrangement of the highly dynamic podocyte actin cytoskeleton. Proteins regulating the plasticity of the podocyte actin cytoskeleton are therefore of critical importance for sustained kidney barrier function. Synaptopodin is an actin-associated protein essential for the integrity of the podocyte actin cytoskeleton because synaptopodin-deficient mice display impaired recovery from protamine sulfate-induced foot process effacement and lipopolysaccharide-induced nephrotic syndrome. Moreover, bigenic heterozygosity for synaptopodin and CD2AP is sufficient to induce spontaneous proteinuria and focal segmental glomerulosclerosis-like glomerular damage in mice. Mechanistically, synaptopodin induces stress fibers by blocking the proteasomal degradation of RhoA. Here we show that synaptopodin directly binds to IRSp53 and suppresses Cdc42:IRSp53:Mena-initiated filopodia formation by blocking the binding of Cdc42 and Mena to IRSp53. The Mena inhibitor FP(4)-Mito suppresses aberrant filopodia formation in synaptopodin knockdown podocytes, and when delivered into mice protects against lipopolysaccharide-induced proteinuria. The identification of synaptopodin as an inhibitor of Cdc42:IRSp53:Mena signaling defines a novel antiproteinuric signaling pathway and offers new targets for the development of antiproteinuric therapeutic modalities.
 ...
PMID:Synaptopodin protects against proteinuria by disrupting Cdc42:IRSp53:Mena signaling complexes in kidney podocytes. 1756 80

LDL-apheresis (LA) was originally used for familial hyperlipidemia, and then in Japan extended to use for the treatment of patients with peripheral arterial disease (PAD) and nephrotic syndrome due to steroid-resistant focal glomerular sclerosis (FGS). The reason why this treatment is applicable for these disorders is due to the fact that LA exerts its favorable effects beyond the lipid-lowering effect. The main underlying mechanisms, for example, in the case of LA application in patients with PAD are: (1) improvement of hemorheology, (2) improvement of endothelial dysfunction, (3) elevations of serum levels of NO and bradykinin, (4) increase in serum levels of vascular endothelial growth factor, and (5) reduction of adhesion molecules on monocytes. Furthermore, we have reported that LA could have anti-inflammatory effects because LA reduces serum levels of P-selectin, which is known to play an important role in the development of atherosclerosis as well as a reduction of serum C-reactive protein levels as standard biomarker of atherosclerosis. Massive proteinuria is also an important challenge in nephrology. The possible mechanisms besides removal of toxic lipids are the reduction of the vasoconstrictive prostanoid and thromboxane A2 (TXA2) and an improvement in macrophage function evidenced by a significant amelioration of interleukin-8 production by lipopolysaccharide-stimulated peripheral blood mononuclear cells. It is intriguing to note that in terms of pharmacodynamics, LA improves steroid and cyclosporine uptake into lymphocytes. Although there are no randomized controlled trials, it is clear that LA has various effects beyond lowering lipids. Making the device more concise and changing it into a whole blood adsorption type, we need to collect more clinical cases and to study the underlying mechanisms further.
 ...
PMID:Applications of LDL-apheresis in nephrology. 1817 56


1 2 Next >>