Identification and immunohistochemical localization of macrophage migration inhibitory factor in human kidney

Imamura, Kiichi; Nishihira, Jun; Suzuki, Masaki; Yasuda, Kazue; Sasaki, Satoshi; Kusunoki, Yukihiro; Tochimaru, Hiroyuki; Takekoshi, Yasuo

doi:10.1080/15216549600201883

Cited by 51 publications

(51 citation statements)

References 19 publications

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“…In the kidney, MIF-whose role in host inflammatory and immune responses is well established [35]-is produced not only by mesangial cells and infiltrating macrophages [36] but also by glomerular epithelial and endothelial cells and by tubular cells [37]. Unlike IL6 or CD40, MIF levels were mainly influenced by oxidised LDL, as confirmed by immunocytochemistry.…”

Section: Discussionmentioning

confidence: 82%

Effects of different LDL particles on inflammatory molecules in human mesangial cells

et al. 2008

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Aims/hypothesis Inflammation is a mechanism of glomerular damage in chronic glomerulopathies. LDL may increase the production of inflammatory cytokines in renal tissues. However, the relative role of native, oxidised and glycated LDL in promoting this process has been only partially elucidated. Methods We tested the inflammatory and proapoptotic effects of native, oxidised and glycated LDL in human mesangial cells (HMCs) by measuring levels of IL6, CD40 and macrophage migration inhibitory factor (MIF) genes, MIF protein, release of IL6, soluble CD40, fibronectin and laminin, early and late apoptosis, and extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation. Results IL6 and CD40 mRNA were dose-dependently upregulated by all three species; this was closely paralleled by their increased release. MIF mRNA was potently stimulated by modified LDL, as confirmed by immunostaining. Fibronectin and laminin release was stimulated by both oxidised and glycated, but not native, LDL. All LDL species induced some increase in late, but not early, apoptosis, and similarly activated JNK2/3 phosphorylation; in contrast, ERK1/2 phosphorylation was more strongly upregulated by oxidised than either native or glycated LDL.Conclusions In HMCs, the production and release of IL6 and CD40 is stimulated by both native and modified LDL, while MIF is more strongly stimulated by oxidised LDL. Regarding the pattern of mesangial expansion, fibronectin and laminin are upregulated by oxidised and glycated LDL. Apoptosis, if modest, is induced by all species. Intracellular signalling of native and modified LDL involves JNK2/3 and, perhaps more specifically, ERK1/2. Tight control of the lipid profile may be useful in preserving kidney function in patients with metabolic alterations.

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Section: Discussionmentioning

confidence: 82%

Effects of different LDL particles on inflammatory molecules in human mesangial cells

et al. 2008

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“…3), in agreement with previous data concerning normal human kidneys. 19) Furthermore, chemokines, which are normally induced by macrophages such as MCP-1 and TNF-α, were not elevated in our microarrays. In other words, there was no evidence of proinflammatory cytokine involvement in relation to microalbuminuria in the kidney of early 8-weeks-old db/db mice.…”

Section: Resultsmentioning

confidence: 98%

Macrophage Migration Inhibitory Factor Is a Possible Candidate for the Induction of Microalbuminuria in Diabetic <i>db</i>/<i>db</i> Mice

Watanabe

Tomioka

Doshi

et al. 2013

Biological & Pharmaceutical Bulletin

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Preventing the onset of microalbuminuria in diabetic nephropathy is a problem that needs urgent rectification. The use of a mouse model for diabetes is vital in this regard. For example, db/db mice exhibit defects in the leptin receptor Ob-Rb sub-type, while the ob/ob strain exhibits defects in the leptin ligand. These mouse strains demonstrate type 2 diabetes, either with or without microalbuminuria, respectively. The purpose of the present study was to use DNA microarray technology to screen for the gene responsible for the onset of diabetic microalbuminuria. Using Affymetrix Mouse Gene ST 1.0 arrays, microarray analysis was performed using total RNA from the kidneys of ob control, ob/ob, db/m, and db/db mice. Microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that transcription of the macrophage migration inhibitory factor (MIF) gene was significantly enhanced in the kidneys of db/db mice. Western blotting showed that levels of MIF protein was enhanced in the kidneys of both diabetic db/db and ob/ob mice. On the other hand, elevation of urinary MIF excretion detected by enzyme-linked immunosorbent assay (ELISA) was only in db/db mice and preceded the onset of microalbuminuria. Immunofluorescence studies revealed that MIF was expressed in mouse kidney glomeruli. While MIF expression was enhanced in the diabetic kidneys of both mouse strains, the elevated secretion from db/db mouse kidneys may be responsible for initiating the onset of microalbuminuria in diabetic nephropathy.Key words macrophage migration inhibitory factor; diabetic nephropathy; microalbuminuria; db/db mouse; ob/ob mouse Diabetic nephropathy is the primary causative disease leading to dialysis in Japan.1) The cumulative incidence of nephropathy after 30 years of post-pubertal diabetes was reported to be significantly higher in type 2 diabetic patients (44.4%) than in type 1 diabetic patients (20.2%).2) However, diabetic nephropathy does not occur in all patients with type 2 diabetes mellitus, implying that there might be an unknown underlying mechanism to prevent the onset of diabetic nephropathy. Establishing the identity of such a mechanism is of vital importance.It is thought that the onset of microalbuminuria, considered to be a marker of early diabetic nephropathy, must be suppressed in order to inhibit the onset and aggravation of nephropathy in type 2 diabetes. Two murine strains are available as an animal model for type 2 diabetes: db/db mice in which microalbuminuria develops at 8 weeks of age 3); and ob/ob mice that do not develop microalbuminuria at all. It is thought that a gene cluster associated with the onset of microalbuminuria could therefore be identified by comparing differences in gene expression between these two mouse strains, without considering a specific disease-developing mechanism underlying microalbuminuria.The purpose of this study was therefore to identify a gene associated with the onset of microalbuminuria in the type 2 diabetic model mouse using a DNA microarray appro...

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“…MIF is a potent pro-inflammatory cytokine whose production is transcriptionally regulated by glucose [3,4,6,7]. Experimental data from T1D patients and animal models also suggests a role for MIF in T1D development [9][10][11][12].…”

Section: Discussionmentioning

confidence: 99%

“…It is expressed in numerous types of tissues, including pancreatic B-cells and cells of the immune system (T and B cells, monocytes, macrophages) [3,4]. A unique property of MIF is its release from macrophages after stimulation with glucocorticoid hormones.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus

Martin¹,

Savage²,

Carson

et al. 2010

Diabetic Medicine

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Aims Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine whose production is transcriptionally regulated by glucose. Experimental data from both Type 1 diabetes mellitus (T1D) patients and animal models suggests a role for MIF in the development of T1D. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the MIF gene and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a combination of case-control and family-based association analyses in order to assess the association of MIF htSNPs with the development of T1D in a white population.Methods All exons, introns and approximately 3 kb upstream and downstream of the MIF gene were screened for DNA polymorphisms in 46 individuals using DNA sequencing. Genotyping of the htSNPs was performed in 432 cases, 407 control subjects and 290 T1D parent-offspring trios, using Taqman, Sequenom, Pyrosequencing and fluorescence-based microsatellite technologies.Results Twenty-three polymorphisms (two novel) with a minor allele frequency > 10% were identified. Four MIF htSNPs (rs875643 G>A, rs7388067 C>T, rs5844572 ) ⁄ CATT, rs6003941 T>G) were identified. Allele and haplotype frequencies were similar between case and control groups (P > 0.6 by permutation test) and assessment of allele transmission distortion from informative parents to affected offspring also failed to find an association. Stratification of these analyses for age-at-onset and human leukocyte antigen (HLA)-DR risk group (DR3 ⁄ DR4) did not reveal any significant associations.Conclusions It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population.

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Identification and immunohistochemical localization of macrophage migration inhibitory factor in human kidney

Cited by 51 publications

References 19 publications

Effects of different LDL particles on inflammatory molecules in human mesangial cells

Effects of different LDL particles on inflammatory molecules in human mesangial cells

Macrophage Migration Inhibitory Factor Is a Possible Candidate for the Induction of Microalbuminuria in Diabetic <i>db</i>/<i>db</i> Mice

Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus

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