PMID- 9218606 OWN - NLM STAT- MEDLINE DCOM- 19970805 LR - 20031114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 159 IP - 2 DP - 1997 Jul 15 TI - Chemokine expression in experimental tubulointerstitial nephritis. PG - 870-6 AB - 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. FAU - Tang, W W AU - Tang WW AD - Department of Pathology, Amgen Inc., Thousand Oaks, CA 91320, USA. FAU - Qi, M AU - Qi M FAU - Warren, J S AU - Warren JS FAU - Van, G Y AU - Van GY LA - eng PT - Journal Article PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokines) RN - 0 (RNA, Messenger) RN - 58-60-6 (Puromycin Aminonucleoside) SB - IM MH - Animals MH - Chemokines/*biosynthesis MH - Immunohistochemistry MH - Kidney Cortex/*immunology/pathology MH - Nephritis, Interstitial/chemically induced/*immunology MH - Puromycin Aminonucleoside MH - RNA, Messenger/analysis MH - Rats MH - Rats, Inbred Lew EDAT- 1997/07/15 00:00 MHDA- 1997/07/15 00:01 CRDT- 1997/07/15 00:00 PHST- 1997/07/15 00:00 [pubmed] PHST- 1997/07/15 00:01 [medline] PHST- 1997/07/15 00:00 [entrez] PST - ppublish SO - J Immunol. 1997 Jul 15;159(2):870-6.