title: Chemokine expression in experimental tubulointerstitial nephritis.
abstract: Chemokines may be important in the pathogenesis of leukocyte infiltration in tubulointerstitial nephritis associated with glomerular disease. We studied the renal cortical expression of the C-C (macrophage inflammatory protein-1alpha (MIP-1alpha)), monocyte chemotactic protein-1 (MCP-1), and RANTES) and C-X-C (interferon-inducible protein-10 (IP-10), MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)) chemokines 4, 6, 8, 10, 14, and 21 days after the induction of puromycin aminonucleoside (PAN) nephrosis. There was a 7- to 10-fold increase in the steady state mRNA expression of IP-10 and MCP-1 in the renal cortex of rats 6 to 8 days after the administration of PAN that declines thereafter reaching control values by day 21. The site of IP-10 and MCP-1 mRNA production was localized to intrinsic tubulointerstitial cells and not to infiltrating monocytes or macrophages. By comparison, there was a low basal expression of RANTES mRNA in the renal cortex of nephrotic rats that did not differ from those of control rats. In contrast, CINC, MIP-2, and MIP-1alpha mRNAs were not detected. Translation of MCP-1 mRNA into protein was confirmed with an ELISA. These changes in chemokine gene expression were associated with a tubulointerstitial T lymphocyte and macrophage infiltration beginning on day 6 that peaked on day 10. Administration of a neutralizing Ab to rat MCP-1 (n = 5) beginning on day 4 resulted in a 45% decline in tubulointerstitial macrophage infiltration from 8.4 +/- 1.3% to 4.6 +/- 0.4% (p < 0.001) on day 6. These data provide evidence that MCP-1, and possibly IP-10, are important in the pathogenesis of monocyte/macrophage infiltration in the tubulointerstitial nephritis associated with PAN nephrosis.
authors.affiliation: Department of Pathology, Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Qi
authors.forename: J S
authors.initials: JS
authors.lastname: Warren
authors.forename: G Y
authors.initials: GY
authors.lastname: Van
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000276:immunology* / Q000473:pathology; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000276:immunology*; D011692:Puromycin Aminonucleoside; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D011692:Puromycin Aminonucleoside