EXPRESSION OF LEUKOCYTE CHEMOATTRACTANTS BY INTERSTITIAL RENAL FIBROBLASTS - UP-REGULATION BY DRUGS ASSOCIATED WITH INTERSTITIAL FIBROSIS

Interstitial inflammation is a strong predictor of long-term renal dam age. The potential role of renal interstitial fibroblasts in recruitme nt of inflammatory leucocytes into the interstitium is unclear. We hav e thus studied the mRNA expression of several leucocyte chemotactic fa ctors by rat renal interstitial fibroblasts and its modulation by cyto kines. In addition, the effects of two unrelated drugs associated with the development of interstitial fibrosis, namely puromycin aminonucle oside (PAN) and cyclosporin A (CsA), were also studied. Rat renal inte rstitial fibroblasts showed constitutive mRNA expression for the chemo kines monocyte chemoattractant protein 1 (MCP-1) and interferon-induci ble protein 10 (IP-10). In addition, these cells also exhibited consti tutive mRNA expression for cyclophilin B, an immunophilin recently fou nd to have leucocyte chemoattractant properties. The inflammatory cyto kine tumour necrosis factor-alpha up-regulated IP-10 and MCP-1 mRNA ex pression (10- and four-fold, respectively), but had no effect on cyclo philin B mRNA levels. IP-10 and MCP-1 produced about a four-fold incre ase in MCP-1 and cyclophilin B mRNA expression, but did not affect IP- 10 mRNA. PAN caused an augmentation in IP-10, MCP-1 and cyclophilin B mRNA levels (12-, 9.5, and two-fold, respectively), while CsA increase d only cyclophilin B mRNA in a dose-dependent manner. In conclusion, r at renal interstitial fibroblasts express mRNA for chemotactic factors and this expression is up-regulated by inflammatory cytokines, PAN an d CsA. The present findings suggest that renal interstitial fibroblast s may play an active role in the recruitment of inflammatory leucocyte s into the interstitium.