Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines participate in leukocyte infiltration, which plays a major role in glomerular injury during immune complex glomerulonephritis (IC-GN). Because target cell expression of chemokine receptors (CCR) is thought to mediate leukocyte migration, the expression pattern of chemokines and CCR in a model of IC-GN was examined. The transient course and predominant glomerular pathology of this model allows the examination of both the induction and resolution phases of IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2 wk, but resolved after 4 wk. This was associated with glomerular IC deposits and mesangial proliferation. Glomerular macrophage infiltration was prominent at 1 and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein-1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control levels at weeks 2 and 4. The expression was localized to glomeruli by in situ hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4. Expression of CCR5 was located to the glomerulus by in situ hybridization and quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and CCR5 are expressed early and are already downregulated at the peak of proteinuria and leukocyte infiltration. Resolution of glomerulonephritis is associated with a return to baseline of chemokine and CCR expression. Therefore, it is concluded that glomerular MCP-1 and RANTES production directs circulating leukocytes that express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated.
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PMID:Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. 1131 50

Immune complex glomerulonephritis (GN) often deteriorates during infection with viruses and bacteria that, in contrast to mammals, have DNA that contains many unmethylated CpG motifs. Balb/c mice with horse apoferritin-induced GN (HAF-GN) were treated with either saline, CpG-oligodeoxynucleotides (ODN), or control GpC-ODN. Only CpG-ODN exacerbated HAF-GN with an increase of glomerular macrophages, which was associated with massive albuminuria and increased renal MCP-1/CCL2, RANTES/CCL5, CCR1, CCR2, and CCR5 mRNA expression. CpG-ODN induced a Th1 response as indicated by serum anti-HAF IgG(2a) titers, mesangial IgG(2a) deposits, and splenocyte IFN-gamma secretion. Messenger RNA for the CpG-DNA receptor Toll-like reeptor 9 (TLR9) was present in kidneys with HAF-GN but not in normal kidneys. The source of TLR9 mRNA in HAF-GN could be infiltrating macrophages or intrinsic renal cells, e.g., mesangial cells; but, in vitro, only murine J774 macrophages expressed TLR9. In J774 cells, CpG-ODN induced the chemokines MCP-1/CCL2 and RANTES/CCL5 and the chemokine receptors CCR1 and CCR5. It is concluded that CpG-DNA can aggravate preexisting GN via a shift toward a Th1 response but also by a novel pathway involving TLR9-mediated chemokine and chemokine receptor expression by macrophages, which may contribute to the enhanced glomerular macrophage recruitment and activation. This mechanism may be relevant during infection-triggered exacerbation of human immune-complex GN and other immune-mediated diseases in general.
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PMID:Bacterial CpG-DNA aggravates immune complex glomerulonephritis: role of TLR9-mediated expression of chemokines and chemokine receptors. 1253 32

The chemokine CC chemokine ligand (CCL)5/RANTES as well as its respective receptor CCR5 mediate leukocyte infiltration during inflammation and are up-regulated early during the course of glomerulonephritis (GN). We tested the effects of the two CCL5/RANTES blocking analogs, Met-RANTES and amino-oxypentane-RANTES, on the course of horse apoferritin (HAF)-induced GN. HAF-injected control mice had proliferative GN with mesangial immune complex deposits of IgG and HAF. Daily i.p. injections of Met-RANTES or amino-oxypentane-RANTES markedly reduced glomerular cell proliferation and glomerular macrophage infiltration, which is usually associated with less glomerular injury and proteinuria in HAF-GN. Surprisingly, however, HAF-GN mice treated with both analogs showed worse disease with mesangiolysis, capillary obstruction, and nephrotic range albuminuria. These findings were associated with an enhancing effect of the CCL5/RANTES analogs on the macrophage activation state, characterized by a distinct morphology and increased inducible NO synthetase expression in vitro and in vivo, but a reduced uptake of apoptotic cells in vivo. The humoral response and the Th1/Th2 balance in HAF-GN and mesangial cell proliferation in vitro were not affected by the CCL5/RANTES analogs. We conclude that, despite blocking local leukocyte recruitment, chemokine analogs can aggravate some specific disease models, most likely due to interactions with systemic immune reactions, including the removal of apoptotic cells and inducible NO synthetase expression.
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PMID:CC chemokine ligand 5/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration. 1275 47