DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver

Reza Zolfaghari, Qiuyan Chen, A. Catharine Ross

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)G578-G588
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number5
DOIs
StatePublished - Sep 1 2012

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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