We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Abstract. A number of experimental models of colitis have been proposed. However, few studies have presented T helper-2 (Th-2) type colitis models that substitute for human ulcerative colitis (UC). In recent years, the murine oxazolone (OXA)-induced colitis model came to be accepted as a Th-2 type model, but it has yet to be used in any pharmacological study. In the present study, we modified the OXA-induced colitis model in BALB / C mice to evaluate the efficacy of treatments for UC. Colitis was induced by intrarectal administration of OXA solution (7.5 mg / mL in 40% ethanol) in a BALB / C strain that is known to favor Th-2 immune responses. A lower mortality rate was obtained in the BALB / C strain than was found in the original method. Histological examination showed that there were morphological similarities to human UC. Increased mRNA expression of interleukin-13, a Th-2 cytokine, was observed in mesenteric lymph nodes. Intrarectal administration of 5-aminosalicylic acid or sodium prednisolone phosphate resulted in a significant improvement in the colitis. These results suggest that the OXA-induced colitis model in the BALB / C strain provides a new way to evaluate the efficacy of therapeutic agents for UC.

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