Expression of leucocyte chemoattractants by interstitial renal fibroblasts: up-regulation by drugs associated with interstitial fibrosis

Abstract

Abstract 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.