Interleukin-11 (IL-11) is a multifuctional cytokine with anti-inflammatory activity. The effect of IL-11 was studied in an experimental model of necrotizing glomerulonephritis induced in Wistar Kyoto rats by an injection of anti-glomerular basement membrane antibody (nephrotoxic serum). Intraperitoneal injection was chosen as the route of IL-11 administration in all experiments. ...

The renin angiotensin system (RAS) has been implicated in tubulointerstitial injury in a range of clinical and experimental settings. Angiotensin II, the major effector molecule of the RAS, in addition to its effects on systemic blood pressure and intrarenal hemodynamics, also acts as a local hormone and growth factor to ...

The term hemolytic uremic syndrome (HUS) was first introduced to describe a heterogeneous group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Substantial progress has been made in our understanding of the etiology and pathogenesis of HUS. This article reviews some of the classic and new ...

Activated macrophages (M(phi)) isolated from inflamed glomeruli or generated by interferon-gamma and lipopolysaccharide treatment in vitro induce glomerular mesangial cell apoptosis by hitherto incompletely understood mechanisms. In this report we demonstrate that nitric oxide-independent killing of co-cultured mesangial cells by interferon-gamma/lipopolysaccharide-activated M(phi) is suppressed by binding/ingestion of apoptotic cells and ...

BACKGROUND: Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both B7-1 and B7-2 costimulatory molecules, protects the kidney during acute ischemia/reperfusion injury. This study investigated whether and how B7-1 and/or B7-2 proteins are involved in renal ischemia/reperfusion injury (IRI). METHODS: Uninephrectomized rats were submitted to warm renal ischemia (30 ...

The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8(+) T-cytotoxic 1 (Tc1) cells and macrophages into ...

Midkine (MK) is a multifunctional heparin-binding protein and promotes migration of neutrophils, macrophages, and neurons. In the normal mouse kidney, MK is expressed in the proximal tubules. After renal ischemic reperfusion injury, its expression in proximal tubules was increased. Immediate increase of MK expression was found when renal proximal tubular ...

Patients with chronic renal failure suffer from defective host defenses which are directly the result of the renal impairment, in addition to those dependent on the primary illness leading to the renal failure. The mechanisms underlying the defective responses in phagocytic cells, lymphocytes and antigen processing are likely due to ...

Epithelial-mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial- mesenchymal interactions during kidney development. ...

Angiotensin (Ang) II, the main peptide of the renin angiotensin system (RAS), is a renal growth factor, inducing hyperplasia/hypertrophy depending on the cell type. This vasoactive peptide activates mesangial and tubular cells and interstitial fibroblasts, increasing the expression and synthesis of extracellular matrix proteins. Some of these effects seem to ...

BACKGROUND: Macrophage accumulation is a prominent feature in many forms of glomerulonephritis. Local proliferation of macrophages within the kidney has been described in human and experimental glomerulonephritis and may have an important role in augmenting the inflammatory response. The current study examined the relationship between local macrophage proliferation and renal ...

Deposition of calcium oxalate (CaOx) crystals in the renal interstitium is common in humans with primary oxalosis and secondary hyperoxaluria, as well as in kidneys of rats with CaOx nephrolithiasis. In vivo, macrophages and multinucleated giant cells mostly encapsulate these crystals. To investigate whether macrophages are able to dispose of ...

BACKGROUND/AIMS: Activator protein-2 (AP-2) is an important transcription factor for activation of growth- and inflammatory-associated genes. To detect AP-2 in the mesangium, the expression level of AP-2 was examined in cultured mesangial cells in response to various cytokines and prostaglandins. The level was also observed in kidney tissue samples obtained ...

Haemolytic uraemic syndrome (HUS), which is caused by Shiga toxin (Stx)-producing Escherichia coli, is the commonest cause of acute renal failure in childhood. It is widely believed that HUS develops following the release of Stx, an AB5 toxin that inhibits protein synthesis and has a direct toxic effect on the ...

BACKGROUND: Hyperlipidemia accelerates the progression of glomerular disease, and lipoproteins bind glomerular mesangial cells (MC) and induce proliferation and cytokine expression. In the vessel wall, the binding of lipoproteins to endothelial cells is markedly enhanced by lipoprotein lipase (LpL), synthesized by the underlying smooth muscle cells. While it is known ...

Renal infiltration with macrophages and monocytes is a well-recognized feature of not only immune, but also nonimmune kidney disease. This review focuses on the investigations that have shown accumulation of immunocompetent cells in experimental models of acute and chronic ischemia, protein overload, hypercholesterolemia, renal ablation, obstructive uropathy, polycystic kidney disease, ...

We examined the role of inflammation in the development of renal interstitial fibrosis in Zucker obese rats, which rapidly present kidney lesions in the absence of hypertension and hyperglycemia. Type I and III collagens were quantified using a polarized light and computer-assisted image analyzer. The expression of mRNA encoding matrix ...

Apoptosis, a programmed form of cell death, is an important mechanism that maintains cellular homeostasis. The cellular content of tissues is regulated by a balance between cell proliferation and cell loss. Apoptosis is important not only in physiological conditions but in pathological processes as well. Apoptosis has been implicated in ...

BACKGROUND: The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS: Rat renal tubular epithelial cells (NRK-52E) were subjected ...

Renal osteodystrophy is the major cause of skeletal morbidity in dialysis patients. It is characterized by beta(2)-microglobulin (beta(2)M) amyloid deposition at the osteoarticular sites and a destructive arthropathy. beta(2)M is present on the surface of all nucleated cells as the small extracellular subunit of the major histocompatibility complex (MHC) class ...

The aim of this study was to investigate whether apoptosis contributes to nephrotoxicity caused by amphotericin B (AmB). By detecting apoptosis-specific DNA fragmentation, it is demonstrated that proximal tubular cells (LLC-PK(1)) and medullary interstitial cells (RMIC) respond with programmed cell death when treated with therapeutic doses of AmB. Concomitant application ...

The caspase family is central to the proteolytic events of apoptosis. In particular, caspase-3 plays a key role in the execution of apoptosis. However, the importance of caspase-3 in renal cell apoptosis during kidney scarring has not been established. Here, nephrotoxic nephritis (NTN) was induced in Wistar Kyoto rats by ...

Leukocyte recruitment to the kidney in immune complex disease like systemic lupus erythematosus (SLE) is mediated in part by local expression of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Recent studies from this laboratory demonstrated that cross-linking Fc gammaR on lymphocytes causes release of a soluble factor that induces monocyte ...

Renal diseases are in many cases associated with the presence of increased numbers of apoptotic cells in the kidney. Apoptosis has been proposed as an important mechanism involved in the resolution of a proliferative response. Furthermore, recent studies indicate its possible involvement in progression of renal disease, leading to sclerosis. ...

Acute renal failure (ARF) can be defined as a sudden loss of renal function and is a common and serious clinical problem. There are many causes of ARF but the most common cause results from injury to the renal tubular epithelial cells (RTECs). RTECs can be injured by schemia or ...

It has been recently recognized that besides its vasoactive actions Angiotensin II (Ang II) exerts various immunomodulatory effects that may contribute to renal injury and to the progression of renal disease. Consistent with this concept, Ang II facilitates macrophage recruitment into the kidney either directly or through the-upregulation of different ...

Visceral glomerular epithelial cells (GECs) are involved in the maintenance of the filtration barrier and may play a role in immune responses. Cytokines may act on GECs and we wished to test this in vitro. Vascular endothelial growth factor (VEGF) is a specific product of the GEC that may play ...

Macrophage accumulation is a prominent feature in most types of human glomerulonephritis. In particular, tubulointerstitial macrophage accumulation correlates with the degree of renal dysfunction and is predictive of disease progression. Depletion studies have shown that macrophages can induce glomerular injury in experimental glomerulonephritis. Moreover, recent studies targeting chemokines and adhesion ...

All progressive renal diseases are the consequence of a process of destructive fibrosis. This review will focus on tubulointerstitial fibrosis, the pathophysiology of which will be divided into four arbitrary phases. First is the cellular activation and injury phase. The tubules are activated, the peritubular capillary endothelium facilitates migration of ...

Mesangial cells play an active role in the inflammatory response to glomerular injury. We have studied in cultured human mesangial cells (CHMC) several effects of 9-cis retinoic acid (9-cRA), an activator of both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). 9-cRA inhibited foetal calf serum-induced CHMC proliferation. It ...

Immune-mediated mesangial cell injury can be triggered by various mechanisms including the trapping of immune complexes, binding of specific antibodies to mesangial cells or indirect binding of immune complexes to mesangial cells via specific receptors. These receptors include specific receptors for IgG or IgA and complement receptors. Interactions of immune ...

BACKGROUND: Galectins are characterized by specific affinity for beta-galactoside sugars, and they play a role in diverse biological processes, including cell adhesion, cell proliferation, and apoptosis. Galectin-1, -3, and -9 have been implicated in modulating the immune response. METHODS: Nephrotoxic serum nephritis, which is characterized by crescent formation and glomerular ...

Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (ANCA + RV) and are believed to contribute to necrotizing extracapillary damage, their precise role is not yet completely understood, especially in humans. The goal of this study was to provide ...

This study investigated whether focal atrophy is a degenerative process of a whole tubule or tubular blockade as partial intratesticular degeneration. Serial section analyses of testicular tissue from 19 men with different andrologic diseases were examined. From every fifth section of any series, defined areas were viewed under a light ...

Apoptosis and extracellular matrix-cell interactions in kidney disease. Extracellular matrix (ECM)-cell interactions have major effects on phenotypic features such as cell growth, differentiation, and gene expression. Apoptosis is an active form of cell death that is crucial for maintaining an appropriate number of cells as well as tissue organization. Recent ...

CD44 is an adhesion molecule involved in a wide range of cell-cell and cell-matrix interactions. The standard form of CD44 (CD44S) is a 85-90-kD glycoprotein, but alternative splicing of RNA encoding 10 variable exons (V1-V10) can give rise to many different CD44 variant protein isoforms of higher molecular weight. CD44 ...

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of ...

Glomerular lesions in lupus nephritis have been extensively studied in recent decades, but much less attention has been paid to the tubulo-interstitial compartment. The aim of this study was to contribute to the understanding of the pathogenesis of tubulo-interstitial lesions in lupus nephritis by analysing their incidence, character, and their ...

Mutual interaction between the metanephric mesenchyme (MM) and the ureteric bud (UB) in the developing kidney leads to branching morphogenesis and the formation of the ureteric tree. A UB-derived cell line, stimulated by conditioned medium derived from an embryonic MM cell line (or, similarly, by 10% fetal calf serum), forms ...

CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the possible ...

PURPOSE: Complete ureteral obstruction (CUTO) in the fetal kidney induces tubular and glomerular cysts, interstitial fibrosis, and halts renal development. Previous studies have shown that apoptosis is a predominant mechanism in the chronically injured kidney following obstruction, but the precise cellular and molecular mechanisms are poorly understood. MATERIALS AND METHODS: ...

The role of bacterial contamination of dialysis water with respect to chronic inflammatory diseases associated with long-term hemodialysis therapy has been greatly underestimated in the last two decades. In the present article, recent multicenter studies assessing the bacteriological quality of water and dialysate are discussed. In addition, we describe that ...

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response ...

Injury mechanisms activated by the hemodynamic adaptations to nephron loss are considered to represent a final common pathway that underlies the progressive nature of chronic renal disease. In this article, we review experimental evidence that the induction of cell adhesion molecule, cytokine and profibrotic growth factor gene expression and the ...

Crescentic glomerulonephritis (GN) is the histopathological correlate of the clinical syndrome of rapidly progressive glomerulonephritis. Glomerular crescent formation complicates proliferative forms of GN and indicates severe disease with a poor renal prognosis. In the past 10 years evidence from experimental models of GN and from human disease has accumulated suggesting ...

BACKGROUND: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established. METHODS: ...

Cell death is central to many physiological and pathological processes. As tissue reactions to the two forms of cell death, necrosis and apoptosis, differ, it is critical to distinguish between them. Although ultrastructure is still the definitive means of assessing this, there are very few in vivo studies. Administration of ...

The role of cell cycle regulatory proteins in progression is elucidated. Human renal biopsy data show amelioration and even regression of structural injury with interventions. Data implicate new mechanisms of the renin-aldosterone-angiotensin system in progressive injuries, including immune modulation and a direct effect of aldosterone on progression. New approaches and ...

The complex interactions of glomerular and tubular epithelial cells with the basal laminae play a critical role in renal function. Disruption of these interactions has been widely implicated in glomerular diseases and acute renal failure. MDC are a large family of membrane-bound proteins containing metalloprotease, disintegrin (integrin interaction sites), and ...

The development and progression of sclerosis is determined by complex interactions of many mechanisms, including direct hemodynamic actions, modulation of glomerular cell injury, and growth factor actions. The interplay of these factors determines the balance of cell growth and proliferation versus cell death by necrosis or apoptosis, and the balance ...