Elevated macrophage migration inhibitory factor (MIF) levels in the urine of patients with focal glomerular sclerosis

Department of Internal Medicine, Division of Nephrology and Endocrinology, Nihon University School of Medicine, Tokyo, Japan.
Clinical & Experimental Immunology (Impact Factor: 3.04). 03/2005; 139(2):338-47. DOI: 10.1111/j.1365-2249.2004.02670.x
Source: PubMed


The pathogenesis of focal glomerular sclerosis (FGS) is poorly understood. Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine released from T cells and macrophages, and is a key molecule in inflammation. To examine further the possible role of MIF in FGS, we measured MIF levels in the urine. The purpose of the present study was to evaluate the involvement of MIF in FGS. Urine samples were obtained from 20 FGS patients. The disease controls included 40 patients with minimal-change nephrotic syndrome (MCNS) and membranous nephropathy (MN). A group of healthy subjects also served as controls. Biopsies were performed in all patients prior to entry to the study. The samples were assayed for MIF protein by a sandwich enzyme-linked immunosorbent assay (ELISA). The levels of MIF in the urine of FGS patients were significantly higher than those of the normal controls and patients with MCNS and MN. In contrast, the levels of urinary MIF (uMIF) in patients with MCNS and MN did not differ significantly from normal values. In the present study, attention also focused on the relationship between uMIF levels and pathological features. Among the patients with FGS, uMIF levels were significantly correlated with the grade of mesangial matrix increase and that of interstitial fibrosis. There was also a significant correlation between uMIF levels and the number of both intraglomerular and interstitial macrophages. Although the underlying mechanisms remain to be determined, our study presents evidence that urinary excretion of MIF is increased in FGS patients with active renal lesions.

1 Follower
8 Reads
  • Source
    • "Matsumoto et al. reported that urinary excretion of MIF is increased in patients with focal glomerular sclerosis and that urinary MIF levels, are higher in patients with active glomerular lesions [89]. Immunocytochemical and in situ hybridization studies have shown that MIF is produced by local resident glomerular cells [22], and that administration of a neutralizing anti-MIF antibody dramatically suppresses an immunologically induced disease model of rapidly progressive crescentic glomerulonephritis (GN) [61]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Macrophage migration inhibitory factor (MIF) was originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibited the random migration of macrophages. MIF is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses. Moreover, the pivotal nature of its involvement highlights the importance of MIF to the pathogenesis of various inflammatory disorders and suggests that blocking MIF may be a useful therapeutic strategy for treating these diseases. This paper discusses the function and expressional regulation of MIF in several rheumatic diseases and related conditions.
    12/2010; 2010(2090-1984):106202. DOI:10.1155/2010/106202
  • Source
    • "Therefore, its deleterious effects, including podocyte apoptosis (Tejada et al., 2008) may be exerted in these cells also in an autocrine manner. Macrophage migration inhibitory factor (MIF) is another cytokine which may promote cell injury and which is synthesized by podocytes (Sasaki et al., 2004; Matsumoto et al., 2005). Possibility of an autocrine response to MIF has been proven by recent finding that podocytes from diabetic Pima Indians show an increased expression of the functional MIF receptor CD74, which was further confirmed in cultured human podocytes exposed to high glucose (Sanchez-Nino et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperglycemia and deriving from glomerular hypertension mechanical stress are the key factors underlying pathogenesis of diabetic nephropathy (DN). Multiple direct and secondary effects of both these factors are mediated by complex signaling pathways with extensive interactions. The common signaling pathways stimulated by high glucose and mechanical insult may act in an additive manner, thereby accelerating the cell damage. Podocytes, the cells covering the outer aspect of glomerular basement membrane (GBM), are subjected not only to the load of filtered glucose but also to diverse mechanical forces. Bulging into the Bowman's space, they have no support from the apical side, which makes them particularly susceptible to the effects of mechanical strain. Both high glucose and mechanical stress may impair the protein systems anchoring the podocyte foot processes in GBM, therefore blunting resistance of these cells to mechanical forces. Modulation by these factors of expression and activity of numerous structural and functional proteins results in the (auto)inflammatory responses, dysfunction, apoptosis or necrosis of the podocytes. Loss of the podocytes is irreversible due to their inability to proliferate and to replenish damaged cells. Podocytes are injured early in the course of DN, which, most likely, underlies further glomerular and renal damage in diabetes. This review summarizes the effects of elevated glucose and mechanical stress that seem to be involved in podocyte impairment in diabetes, with particular focus on the possible interactions between these factors.
    Journal of Cellular Physiology 11/2009; 221(2):288-95. DOI:10.1002/jcp.21856 · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: MIF is a proinflammatory cytokine present in preformed stores in human urothelium. In animal models of bladder inflammation, including bacterial cystitis, MIF is up-regulated in the bladder and released from the bladder as a high molecular weight complex. We compared urine MIF amounts in patients with UTI to that in patients without UTI, and we examined and identified MIF-protein complexes in urine. Using enzyme-linked immunosorbent assay we compared MIF levels in the urine of 14 patients with UTI to levels in 16 controls with no UTI. Western blotting under native, denaturing and reducing conditions was done to examine MIF complexes found in urine. Mass spectrometry identified MIF associated proteins in urine, while co-immunoprecipitation confirmed the associations. Mean urine MIF amounts +/- SEM determined by enzyme-linked immunosorbent assay were significantly greater in 14 patients with UTI compared to that in 16 controls (1.96 +/- 0.40 vs 0.59 +/- 0.09 ng/mg creatinine, p <0.01). Western blotting under denaturing conditions showed several high molecular weight complexes (100 to 165 kDa) that increased in UTI urine as well as typical, monomeric MIF (12 kDa). Mass spectrometry identified associated MIF proteins, including ceruloplasmin, albumin and uromodulin. Co-immunoprecipitation confirmed mass spectrometry findings and also identified MIF interaction with alpha-2-macroglobulin. Increased urine MIF amounts in patients with bacterial cystitis support our experimental evidence showing a role for MIF in pelvic visceral inflammation. The novel finding of an association of MIF with other urine proteins suggest that the physiologically relevant form of MIF may be an MIF-protein complex.
    The Journal of Urology 04/2006; 175(4):1523-8. DOI:10.1016/S0022-5347(05)00650-6 · 4.47 Impact Factor
Show more

Preview (2 Sources)

8 Reads
Available from