Inhibition of monocyte chemoattractant protein-1 expression in tubular epithelium attenuates tubulointerstitial alteration in rat Goodpasture syndrome

Background. To examine the role of monocyte chemoattractant protein-1 (MCP- 1) expressed by tubular epithelium in tubulointerstitial alterations in sit u, the level of MCP-1 mRNA in tubular epithelium was lowered selectively in the rat model of Goodpasture syndrome (GPS). Methods. Intravenously administered antisense oligodeoxynucleotide (ODN) is taken up by renal tubular epithelium and has been found to block expressio n of target genes in rats. MCP-1 antisense ODN was injected into GPS rats e very second day from days 27 to 35 after immunization (this represents the time when renal MCP-1 mRNA level was increased and interstitial mononuclear cell infiltration was aggravated). Results. In addition to a reduction in the level of tubular MCP-1 mRNA, ant isense ODN treatment attenuated monocyte infiltration significantly and pre served renal function in GPS rats. However, ODN injection did not affect gl omerular MCP-1 expression and glomerular histopathology, and there were no significant changes in the urinary protein excretion rate. Conclusion. Our findings provide direct evidence that MCP-1. expressed by t ubular epithelium, plays a pivotal role in mediating secondary tubulointers titial alterations in the GPS model.