Both
retinoid status and
inflammation have been shown to control the level of expression of
retinoid homeostatic genes. In the present study, DHRS3, previously shown to possess
retinal reductase activity, was identified by microarray analysis of THP-1 monocytes as a possible gene target of
all-trans-retinoic acid (RA). In these cells, DHRS3
mRNA increased 30- to 40-fold
after treatment with ≤20 nM RA for 24 h, while DHRS3
protein also increased. Of several synthetic
retinoids tested, only
Am580, a RA receptor-α-selective
retinoid, increased DHRS3
mRNA expression. The full-length DHRS3
cDNA was cloned from rat liver and subjected to in vitro transcription-translation. Two major ∼30- and 35-kDa
proteins were detected. In adult rat tissues, DHRS3
mRNA was most abundant in the adrenal gland, liver, and ovary. In the liver, DHRS3 is expressed in hepatocytes and possibly in all liver cells. To evaluate whether DHRS3 is regulated in the liver by RA and/or inflammatory stimuli, we treated rats for 6 h with RA or LPS or both. DHRS3
mRNA was doubled by RA but reduced by >90%
after treatment with LPS in the absence and presence of RA. On the basis of our results, DHRS3
mRNA expression is regulated by RA in a tissue- or cell-type specific manner; the RA-induced increase in DHRS3 may contribute to
retinoid storage; and a reduction of DHRS3 expression in the liver during
inflammation may contribute to the perturbation of whole body
vitamin A metabolism that has previously been shown to occur in conditions of inflammatory stress.