Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction

Background. To extend our previous study of the therapy of the renal lesion s of unilateral ureteral obstruction (UUO) in mice by an inhibitor of inter cellular adhesion molecule-1 (ICAM-1), we investigated the blocking effects of ICAM-1 antisense oligonucleotides (ASONs) on the ICAM-1 expression in m ouse kidney. Methods. First, ICAM-1 ASON was transducted into mouse renal tubular epithe lial cells to investigate the effects of ICAM-1 ASON in vitro. Second, fluo rescein isothiocyanate (FITC)-labeled ICAM-1 ASON was injected intravenousl y to determine the distribution of the ASON in. vivo. Third, the expression of ICAM-1 in kidney and the changes of renal morphology were observed to i nvestigate the therapeutic effects of ICAM-1 ASON on the UUO mice in vivo. Results. The expressions of ICAM-1 in the epithelial cells induced by inter leukin-1 beta were inhibited by ICAM-1 ASON at the dosages of 100 and 200 n mol/L Twenty-four hours after an introvenous injection with FITC-labeled IC AM-1 ASON, the highest level of fluorescein was detected within the proxima l tubules in mouse kidney. Results of immunohistology and Northern blot sho wed that the ICAM-1 expression was markedly reduced in the obstructed kidne y after treatment with ICAM-1 ASON. The ASON also alleviated the infiltrati on of inflammatory cells and accumulation of the extracellular matrix in th e tubulointerstitium of UUO mice without apparent side effects. Conclusion. Our data demonstrate that ICAM-1 ASON is taken up primarily by the proximal tubular cells of mouse kidney. ICAM-1 ASON can selectively inh ibit the ICAM-1 expression of the renal tubular cells both in vitro and in vivo.