The interaction between mesangial cells (MCs) and monocytes/macrophages (Mo/Mo) is an important pathogenic feature of glomerulonephritis. However, its mechanism is not fully elucidated. Studies to date have focused on the interactions through mediators. In the present study, to obtain insight into the mechanism of the interaction between MCs and Mo/Mo, ...

The combination of hemorrhagic pneumonitis and rapidly progressive glomerulonephritis is a characteristic feature of Goodpasture's syndrome (GPS), an autoimmune disease resulting from the interaction of pathogenic anti-collagen type IV (C-IV) antibodies with alveolar and glomerular basement membranes. Lack of a suitable animal model for this fatal disease has hampered both ...

Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and influence ECM synthesis in experimental diabetes. To ...

Excessive production of nitric oxide (NO) and its peroxidant product, peroxynitrite, has been implicated in the pathology of acute and chronic renal failure, and inhibitors of NO production have been shown to exert protective and ameliorative effects against renal epithelial cell damage mediated by enhanced generation of NO. Salviae Miltiorrhizae ...

Most human nephritis is due to glomerular deposition and/or formation of immune complexes (IC). In cultured mesangial cells, Fc receptor stimulation induces proliferation, matrix synthesis, and release of several mediators implicated in the initiation and progression of glomerular injury. Since Ig Fc fragments in vitro modified these phenomena, we studied ...

During inflammation in the glomerulus, the complement of resident myofibroblast-like mesangial cells is regulated by mitosis and apoptosis, but the cellular mechanisms controlling the size of mesangial cell populations have remained obscure. Prompted by studies of development, we sought evidence that macrophages regulate mesangial cell number. Rat bone marrow-derived macrophages ...

BACKGROUND:Mycophenolic acid has been shown to be effective for the prevention and treatment of renal allograft rejection. Rejection episodes were found to be associated with an infiltration of lymphocytes and macrophages/monocytes into the diseased kidney. Expression of RANTES, HLA-DR and ICAM-1 may be important for the pathogenesis of this leukocyte ...

MRL/Mp-lpr/lpr (MRL/lpr) mice develop immune complex glomerulonephritis similar to human lupus. Glomerular mesangial cells are key modulators of the inflammatory response in lupus nephritis. When activated, these cells secrete inflammatory mediators including NO and products of cyclooxygenase perpetuating the local inflammatory response. PGJ2, a product of cyclooxygenase, is a potent ...

BACKGROUND: Cytokines regulate many processes in the immune system and have recently been implicated in normal organogenesis. We previously demonstrated that the archetypal inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) is expressed in the murine metanephros, and exogenous TNF-alpha inhibits nephrogenesis and increases macrophage numbers in vitro (Cale et al., Int ...

Mechanical stresses appear to play a key role in the progression of glomerular diseases that are characterized by increased transcapillary hydraulic pressure. Glomerular mesangial cells proliferate and produce extracellular matrix proteins in vivo in such diseases. Mesangial cell responses to pulsatile mechanical stimuli have been studied extensively in vitro during ...

The distal tubule of the mammalian kidney, defined as the region between the macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functional properties of individual cell types and has led to controversy concerning mechanisms and regulation of ion transport. Recently, ...

Glomerulonephritis is a significant factor fueling the rapid increase in the population of patients with end-stage renal disease. Novel therapeutic strategies targeting specific mechanisms of glomerular destruction are the most reasonable approaches to arrest ongoing injury. In this review, we summarize some of our results obtained in our effort to ...

Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. BACKGROUND: Proteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. However, most ...

Many studies on the etiology of stone disease have focused on the properties of urine that affect crystal nucleation and growth. More recent studies have focused on the properties of the renal epithelium and the role of injury in crystal retention. The latter studies have shown that oxalate exposure per ...

In the past few decades, accumulating evidence has been generated on the central role of the proximal tubular cell in renal injury and dysfunction, such as can be found in some patients with glomerular proteinuria and in chronic renal rejection or following ischaemic insult. Following initial injury or stimulation of ...

Verocytotoxin 1 and 2 (VT1 and 2) produced by verocytotoxin-producing Escherichia coli have been considered to play an important role in the pathogenesis of glomerular and tubular damage in the epidemic form of hemolytic uremic syndrome (HUS). VTs are known to be cytotoxic to culture cells by inhibiting cellular protein ...

Fetal kidneys modulate the allogeneic immune response by a synergistic effect: first, fetal kidney tissue tropism is abrogated by the initial relative lack of adhesion molecules. Second, the reduced expression of major histocompatibility complex (MHC) determinants is less effective in inducing the alloantigen-primed T cell response, which in turn induces ...

BACKGROUND: The pathogenesis of glomerular damage in glomerulonephritis (GN) is not fully understood. Several studies have suggested that reactive oxygen molecules play a role in renal disease. It is known that, during GN, mesangial cells are activated. In a previous study, we demonstrated that in vitro interleukin (IL)-1 plus IL-6 ...

The development of tubulointerstitial fibrosis in inflammatory renal diseases has been linked to disease progression to end-stage renal failure. Understanding the interactions of the factors influencing inflammation and activating the fibrotic process, that is, the inflammatory infiltrate and the resident proximal tubular cells, may lead to a determination of the ...

Work with transgenic animals and in vitro manipulation of organs in culture has highlighted an increasing number of genes that are important in the normal development of the kidney and whose disruption inhibits nephrogenesis. The phenotype seen with some agents resembles that of the congenital renal anomaly renal dysplasia, in ...

Most chronic human kidney diseases are characterized by a final common pathway consisting of interstitial inflammation and ultimately leading to interstitial fibrosis. Within this process, tubular epithelial cells (TECs) play a critical role. Both in vitro and in vivo it has been demonstrated that TECs are an important source of ...

BACKGROUND: Heparin, the multifunctional glycosaminoglycan, has been considered a therapeutic agent for glomerular diseases. Although a number of biological properties are postulated to explain its therapeutic utility, it is unknown whether heparin affects cell survival in the glomerulus. In this report, we investigated the effect of heparin on apoptosis of ...

Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although different causes have been postulated. We investigated ...

We constructed an ex vivo gene transfer system to deliver cytokines into the kidney and circulation using genetically modified renal tubular epithelial cells (TEC). TEC were infected with recombinant retroviruses expressing macrophage (Mphi) growth factors using a retroviral Moloney murine leukemia virus-based MFG vector. These infected TEC have the capacity ...

Tacolimus (FK506) is a potent immunosuppressive agent with significant nephrotoxic properties. FK506 is complexed with an intracellular binding protein FKBP-12. Both the immunosuppressive and nephrotoxic effects may be linked to the inhibitory effect of this complex on calcineurin. The initial phase of FK506 nephrotoxicity is associated with a reduction in ...

To investigate bacterial growth and inflammatory mediator release in the early stage of the immune response, a unilateral acute ascending pyelonephritis was induced in rats by intrabladder inoculation of Escherichia coli. The infected left kidney showed a significant bacterial proliferation, local production of interleukin (IL)-6 and IL-8 as detected by ...

The balance between local offense factors and defense machinery determines the fate of tissue injury: progression or resolution. In glomerular research, the most interest has been on the offensive side, for example, the roles of leukocytes, platelets, complement, cytokines, eicosanoids, and oxygen radical intermediates. There has been little focus on ...

Crescentic glomerulonephritis provides an important therapeutic challenge because of its rapidly progressive course and poor outcome. Studies in animal models have elucidated some of the pivotal pathogenetic mechanisms, and human studies increasingly support the clinical relevance of these animal data. Accumulating evidence suggests that crescentic glomerulonephritis results from a complex ...

BACKGROUND: Verocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli infection is the principal cause of hemolytic uremic syndrome (HUS). The pathogenesis is unclear, and there is a need for animal models. These are impeded by the different distribution of verocytotoxin receptors between species. We have circumvented this restriction using ricin, which gains entry ...

Several lines of evidence show the importance of angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A ...

The majority of patients with rapidly progressive crescentic glomerulonephritis show histologic features of extensive necrosis and focal and segmental proliferation with fibrin production, but little or absent Ig deposition in the glomerulus. This subcategory of the disease, labeled "pauci-immune" glomerulonephritis, has recently been shown to be associated with the presence ...

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in ...

It is generally accepted that the progressive loss of kidney function results from a pathogenic process that is independent of the original etiology, functioning as a final common pathway. Part of this response is characterized by triggering of interstitial infiltration and induction of tubular damage. As a consequence, tubular epithelial ...

This review has highlighted the cytokine network which is involved in renal damage from an initial, even transient, stage to extensive glomerular and tubulointerstitial sclerosis. Studies of a variety of different proliferative glomerulonephritides have documented the prominent role of macrophages in infiltrating mesangium, subendothelial area and crescentic formation. Thus, they ...

Cytokines, chemokines, and growth factors are overexpressed by renal parenchymal cells and by infiltrating mononuclear cells in human and experimental lupus nephritis. The importance of cytokines in the pathogenesis of lupus nephritis has been established using spontaneous mouse models of systemic lupus erythematosus (SLE). The actions of these cytokines are ...

Macrophages have a central role in the control of inflammation because, depending on the local microenvironment, they can develop into cells that cause further injury or facilitate tissue repair. Understanding what signals determine whether macrophages develop into cells that promote injury or facilitate repair is one of the most important ...

TGF-beta has several anti-inflammatory properties which may be relevant to prevention of or recovery from acute glomerular inflammation. Using genetically modified mesangial cells and a technique for in vivo macrophage transfer, this article provides evidence for TGF-beta-mediated 'self-defence' of the glomerulus against macrophages. Rat mesangial cells stably transfected with TGF-beta1 ...

The effect of mycophenolate mofetil (MMF) was examined in active Heymann nephritis (HN), an animal model of human membranous nephropathy. HN was induced in Lewis rats with Fx1A/complete Freund's adjuvant (CFA), and controls only received CFA. The induction of HN was prevented by MMF (30 mg/kg per d) from 0 ...

We studied renal function, glomerular cell proliferation and apoptosis for three months after uninephrectomy (UNX) in young, male, spontaneously hypertensive rats (SHR). Apoptosis was assessed by in situ dUTP biotin nick-end labeling method (TUNEL) and by propidium iodide staining. Proliferation rate was determined by immunohistochemistry to proliferating cell nuclear antigen ...

With the gradual elucidation of the cellular and molecular events that underpin the inflammatory process, the pathogenetic complexities of glomerulonephritis are slowly being unravelled. Lipoxygenase-derived eicosanoids play important counter-regulatory roles within inflamed glomeruli. Leukotrienes, derived from the 5-lipoxygenase pathway, are potent stimuli for leukocyte infiltration, intrarenal vasoconstriction, and mesangial cell ...

Numerous pathological processes are involved in the renal tubulointerstitial fibrogenic reaction that occurs after ureteral ligation. Central to these maladaptive events is a florid interstitial monocytic infiltration of the tubulointerstitium, which is preceded by a proximal tubular up-regulation of macrophage chemoattractants. Once within the peritubular and periglomerular space, these macrophages ...

Apoptosis is a highly regulated mechanism of cell death. Although apoptosis has a functional role in normal development and tissue homeostasis, aberrant triggering of the process by toxicants may lead to abnormal function or disease. Low level exposures to toxicants that induce apoptosis in kidney may therefore create a critical ...

A common feature to a number of immune and non-immune renal diseases of diverse etiology is the infiltration of the glomerular and tubulointerstitial compartments by infiltrating macrophages. This review will focus on experimental data supporting the role of the infiltrating renal macrophage as a mediator of interstitial fibrosis during the ...

Distinct patterns of cell proliferation and apoptosis have been recognized for tubular, interstitial, and glomerular cells in chronic obstructive uropathy (OU). In many experimental models of OU, tubular cell apoptosis develops quickly after ureter ligation, peaks between 7 and 24 days postobtruction (about 30-fold of control), and tapers thereafter. Apoptosis ...

BACKGROUND: A main function attributed to B cell leukaemia/lymphoma 2 gene (bcL-2) is its ability to confer resistance against apoptosis. In bcl-2 deficient mice, extensive apoptosis occurs during abnormal nephrogenesis, and renal failure is found very quickly after birth. However, the underlying mechanisms remain poorly understood. The aim of the ...

The reaction of the renal epithelium to injury is heterogenous. Some cells die, others survive apparently intact, while others commit to repair. The determinants of these responses appear to depend on signal transduction pathways and molecular responses that is segment specific and interactive. The kidney, as do cells in culture ...

The deposition of immune complexes, followed by activation of complement and/or Fc receptors and generation of chemoattractants, is the most common feature of human glomerulonephritis. Recently we have shown that primary cultured human glomerular mesangial cells (HMC), which are normally negative for IgG Fc receptors, can be stimulated to express ...

BACKGROUND: The progression of chronic renal failure (CRF) is associated with the progressive deletion of renal cells along with the fibrosis of the kidney. We have studied the role of programmed cell death (apoptosis) in the progression of experimental CRF and renal scarring. METHODS: The sub-total (5/6th) nephrectomy (SNx) model ...

Renal tubular cells that are lethally injured after an acute ischemic or nephrotoxic insult to the kidney can die by necrosis or apoptosis. Necrosis is usually the result of overwhelming and severe cellular ATP depletion. In contrast, there are many potential causes of apoptosis in acute renal failure (ARF). These ...

Tubulointerstitial fibrosis is a final common pathway for progressive renal injury in most 'inflammatory' and 'non-inflammatory' glomerulopathies. Indeed, the level of tubulointerstitial fibrosis correlates closely with the degree of chronic renal dysfunction in these settings. An emerging body of evidence suggests that tubule epithelial cells are dynamic players in the ...