Retinoid homeostatic genes are positively and negatively regulated by retinoic acid and lipopolysaccharide‐induced inflammation in liver of vitamin A‐adequate rats

Retinoic acid is both a metabolite of vitamin A and an approved drug. RA has been proposed to have anti‐inflammatory effects, yet some of its actions appear to be proinflammatory. To better understand the interactions of inflammation and RA in the liver, we performed microarray analysis on liver RNA from normally fed female rats treated acutely with placebo (control); RA, 500 μg orally; lipopolysaccharide (50 μg/kg body weight); and RA+LPS concurrently. Liver was collected 6 h later for microarray and qPCR analysis. Statistical Analysis of Microarray (SAM) with a stringent false discovery rate of 1% identified 703 differentially‐expressed genes. RA alone increased the expression of a very small subset of these genes, principally CYP26A1, CYP26B1 and LRAT. The majority of changes occurred in response to LPS, with ~2/3 of these genes reduced and 1/3 increased. Interestingly, several genes known or hypothesized to be involved in retinoid homeostasis were negatively regulated by LPS, with and without RA, including BCMO1, DHRS3, RALDH1, and RALDH3, while two retinoid biosynthetic genes, RDH2 and RALDH2, were significantly upregulated by LPS. These results provide evidence that inflammation rapidly up‐ and down regulates many hepatic mRNAs; however, RA did not significantly suppress expression of proinflammatory genes (NIH CA‐90214)