Interstitial
inflammation is a strong predictor of long-term renal damage. The potential role of renal interstitial fibroblasts in recruitment of inflammatory leucocytes into the interstitium is unclear. We have thus studied the
mRNA expression of several leucocyte
chemotactic factors by rat renal interstitial fibroblasts and its modulation by
cytokines. In addition, the effects of two unrelated drugs associated with the development of interstitial
fibrosis, namely
puromycin aminonucleoside (PAN) and
cyclosporin A (CsA), were also studied. Rat renal interstitial fibroblasts showed constitutive
mRNA expression for the
chemokines monocyte chemoattractant protein 1 (MCP-1) and
interferon-inducible protein 10 (IP-10). In addition, these cells also exhibited constitutive
mRNA expression for
cyclophilin B, an
immunophilin recently found to have leucocyte
chemoattractant properties. The inflammatory
cytokine tumour
necrosis factor-alpha up-regulated IP-10 and MCP-1
mRNA expression (10- and four-fold, respectively), but had no effect on
cyclophilin B mRNA levels. IP-10 and MCP-1 produced about a four-fold increase 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 increased only
cyclophilin B mRNA in a dose-dependent manner. In conclusion, rat renal interstitial fibroblasts express
mRNA for
chemotactic factors and this expression is up-regulated by inflammatory
cytokines, PAN and CsA. The present findings suggest that renal interstitial fibroblasts may play an active role in the recruitment of inflammatory leucocytes into the interstitium.