Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the pathogenesis of glomerulonephritis, acute renal failure, pyelonephritis and other diseases of the kidneys oxygen radicals are involved. Some types of glomerulonephritis are characterized by infiltration of the glomeruli by neutrophils and monocytes which can form oxygen radicals (superoxide, hydrogen peroxide). The increased amount of cAMP in glomeruli can be due to oxygen radicals. Cyclic nucleotides modulate the inflammatory or immune response in glomerular disease and play a part in the action of local mediators of the inflammation. Oxygen radicals act as second messenger for the activation of cytokines via NF-kappaB transcription factor, they stimulate the formation of TNF-alpha, IL-1, IL-6 and influence the expression of monocyte-specific cytokines (CSF-1 and MCP-1). Radicals formed by the system myeloperoxidase--hydrogen peroxide--halogen derivatives activate proteolytic enzymes (proteinases) which break down collagen and other components of the extracellular matrix present in the basal membrane of glomeruli and in the mesangium. Oxygen radicals and proteinases can cause and amplify glomerular damage. Glucocorticoid administration leads to an increased activity of endogenous antioxidant enzymes in the glomerulus and reduced the of lipid peroxidation.
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PMID:[The role of oxygen radicals in the pathogenesis of glomerulonephritis]. 859 8

The reported requirement of functional Toll-like receptor (TLR)4 for resistance to Gram-negative pyelonephritis prompted us to localize the expression of TLR2 and TLR4 mRNA in the kidney at the cellular level by in situ hybridization. The majority of the constitutive TLR2 and TLR4 mRNA expression was found to be strategically located in the renal epithelial cells. Assuming that the TLR mRNA expression is representative of apical protein expression, this suggests that these cells are able to detect and react with bacteria present in the lumen of the tubules. To gain insight in the regulation of TLR expression during inflammation, we used a model for renal inflammation. Renal inflammation evoked by ischemia markedly enhanced synthesis of TLR2 and TLR4 mRNA in the distal tubular epithelium, the thin limb of Henle's loop, and collecting ducts. The increased renal TLR4 mRNA expression was associated with significant elevation of renal TLR4 protein expression as evaluated by Western blotting. Using RT-PCR, the enhanced TLR2 and TLR4 mRNA expression was shown to be completely dependent on the action of IFN-gamma and TNF-alpha. These results indicate a potential mechanism of increased immunosurveillance during inflammation at the site in which ascending bacteria enter the kidney tissue, i.e., the collecting ducts and the distal part of the nephron.
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PMID:In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. 1180 67

This prospective study, performed in 76 children with a urinary tract infection (UTI), evaluates the diagnostic value of procalcitonin (PCT) and proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) in children with acute pyelonephritis documented by dimercaptosuccinic acid scintigraphy (DMSA). Renal parenchymal involvement was assessed by (99m )Tc-DMSA scintigraphy within 7 days of admission. The diagnosis of acute pyelonephritis was confirmed only in patients with reversible lesions on scintigraphy. According to DMSA scan results, patients were divided into two groups, lower UTI or acute pyelonephritis. In acute pyelonephritis, serum PCT level was found to be significantly higher than it is in the lower UTI (p <0.001). Also, significantly higher serum proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) levels were detected in those with acute pyelonephritis than those with lower UTI (p <0.001). We conclude that both serum PCT and proinflammatory cytokine levels may be used as accurate markers for diagnosis of acute pyelonephritis.
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PMID:Proinflammatory cytokines and procalcitonin in children with acute pyelonephritis. 1607 86

TLR4 plays a central role in resistance to pyelonephritis caused by uropathogenic Escherichia coli (UPEC). It has been suggested that renal tubule epithelial cells expressing TLRs may play a key role in inflammatory disorders and in initiating host defenses. In this study we used an experimental mouse model of ascending urinary tract infection to show that UPEC isolates preferentially adhered to the apical surface of medullary collecting duct (MCD) intercalated cells. UPEC-infected C3H/HeJ (Lps(d)) mice carrying an inactivating mutation of tlr4 failed to clear renal bacteria and exhibited a dramatic slump in proinflammatory mediators as compared with infected wild-type C3H/HeOuJ (Lps(n)) mice. However, the level of expression of the leukocyte chemoattractants MIP-2 and TNF-alpha still remained greater in UPEC-infected than in naive C3H/HeJ (Lps(d)) mice. Using primary cultures of microdissected Lps(n) MCDs that expressed TLR4 and its accessory molecules MD2, MyD88, and CD14, we also show that UPECs stimulated both a TLR4-mediated, MyD88-dependent, TIR domain-containing adaptor-inducing IFN-beta-independent pathway and a TLR4-independent pathway, leading to bipolarized secretion of MIP-2. Stimulation by UPECs of the TLR4-mediated pathway in Lps(n) MCDs leads to the activation of NF-kappaB, and MAPK p38, ERK1/2, and JNK. In addition, UPECs stimulated TLR4-independent signaling by activating a TNF receptor-associated factor 2-apoptosis signal-regulatory kinase 1-JNK pathway. These findings demonstrate that epithelial collecting duct cells are actively involved in the initiation of an immune response via several distinct signaling pathways and suggest that intercalated cells play an active role in the recognition of UPECs colonizing the kidneys.
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PMID:Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. 1698 18

Urinary tract infections may induce severe inflammation, transient impairment in renal function and scar formation, ranging in severity from acute symptomatic pyelonephritis to chronic pyelonephritis, which have a potential to lead to renal failure and death. The present study aimed to investigate the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (leukotriene CysLT1), against Escherichia coli-induced oxidative injury and scarring in renal tissue. Wistar rats were injected 0.1 ml of E. coli (ATCC 25922 10(10) cfu/ml) or saline into left renal medullae. Six rats were assigned as the sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or montelukast immediately after surgery and at daily intervals. Twenty-four hours or one week after E. coli injection, rats were decapitated and the kidney samples were taken for histological examination or determination of renal malondialdehyde, glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples. E. coli inoculation caused significant increases in malondialdehyde level, MPO activity, chemiluminescence levels and collagen content, while GSH level was decreased in the renal tissues (p<0.05-0.001). On the other hand, serum TNF-alpha, LDH, blood urea nitrogen and serum creatinine levels were elevated in the pyelonephritic rats as compared to control group. Leukotriene CysLT1 receptor antagonist montelukast reversed all these biochemical indices, as well as histopathological alterations, that were induced by acute pyelonephritis. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators suggesting a future role for leukotriene CysLT1 receptor antagonists in the treatment of pyelonephritis.
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PMID:Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a selective leukotriene CysLT1 receptor antagonist. 1717 92

Apoptosis of blood monocytes was studied in experimental sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-alpha and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3.5 h and CII (n = 16) with absent activity. Their median survival was 2.0 and 3.5 days, respectively (P = 0.0089). Ex vivo secretion of TNF-alpha from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3.5 h (P = 0.039) and of group A than CII at 48 h (P = 0.010). Median change of caspase-3 activity between 3.5 and 24 h of sampling was 56.1 and -5.8 pmol/min per 10(4) cells for subgroups CI and CII (P = 0.040), respectively. Respective changes between 3.5 and 48 h were 28 981.0 and 0 pmol/min per 10(4) cells (P = 0.036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-alpha.
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PMID:Early apoptosis of blood monocytes is a determinant of survival in experimental sepsis by multi-drug-resistant Pseudomonas aeruginosa. 1748 99

Acute pyelonephritis, frequently caused by Escherichia coli, is a substantial health problem. Plasminogen activator inhibitor type-1 (PAI-1) not only inhibits plasminogen activation but is also involved in cell migration. To determine if it has a role in host defense, we induced pyelonephritis in PAI-1 gene knockout and wild-type mice by intravesical inoculation with uropathogenic E. coli 1677. Bacterial growth was determined on blood agar plates in portions of the kidneys homogenized in sterile saline. Kidney levels of PAI-1 were increased in infected compared to control mice, suggesting a physiological role for PAI-1 during pyelonephritis. The knockout mice had significantly more bacterial outgrowth in kidney homogenates compared to the wild-type mice. Strikingly, higher colony-forming units were accompanied by increased levels of the cytokines TNF-alpha, IL-1beta, and IL-6 in the kidneys of knockout mice, but levels of the chemokines KC and MIP-2 were not different. Remarkably, plasma levels of KC were higher, but renal neutrophil influx was significantly lower, in the knockout than in the wild-type mice. Our study shows that PAI-1 is critically involved in host defense against E. coli-induced acute pyelonephritis, in part, by modulating neutrophil influx.
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PMID:Plasminogen activator inhibitor-1 regulates neutrophil influx during acute pyelonephritis. 1880 31