Gene expression of CC chemokines in experimental acute tubulointerstitial nephritis.
The infiltration of mononuclear leukocytes into glomeruli or the interstitium is a feature in most forms of glomerular diseases. CC chemokines, mostly chemoattractants for mononuclear leukocytes, are molecules that are potentially responsible for the recruitment of these cells in the kidney. We previously reported that the gene expression of six CC chemokines-MCP-1, MCP-3, MIP-1alpha, MIP-1beta, RANTES, and TCA3-was enhanced in a rat model of crescentic glomerulonephritis, the most severe form of glomerulonephritis. In this study we analyzed their gene expression in a model of another type of kidney disease, acute nephrosis accompanied by tubulointerstitial lesions, which is induced by an injection of puromycin aminonucleoside. Because leukocyte infiltration in this model is much more prominent in the interstitium than in glomeruli, we analyzed their gene expression in the renal cortex. On day 3, when the level of urinary protein was slightly but significantly increased but the number of interstitial leukocytes was unchanged, the enhanced expression of mRNAs for MCP-1, MCP-3, and TCA3 was observed. On day 5, the numbers of interstitial monocytes and lymphocytes significantly increased, and the levels of the mRNA expression of the above chemokines were still higher than the control animals, whereas the levels of mRNAs for MIP- 1alpha, MIP-1beta, and RANTES were not higher or were only slightly higher than the control ones. These results suggest that multiple CC chemokines may play a role in the recruitment of leukocytes in this model and that the expression pattern of CC chemokines depends on the type of kidney injury.
Ou
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Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, Tokyo.
Natori
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D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes / Q000737:chemistry; D004195:Disease Models, Animal; D015870:Gene Expression; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000473:pathology; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D009401:Nephrosis / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000473:pathology; D011507:Proteinuria; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019742:Chemokines, CC; D017931:DNA Primers; D015342:DNA Probes; D012333:RNA, Messenger; D011692:Puromycin Aminonucleoside