Page 1 of 31in PresS. Am J Physiol Gastrointest Liver Physiol (December 21, 2006). doi:10.1152/ajpgi.00494.2006 Articles
Lipopolysaccharide Opposes the Induction of Cytochrome P450 CYP26A1 and CYP26B1 Gene Expression by Retinoic Acid in Rat Liver In Vivo
Reza Zolfaghari, Christopher J. Cifelli, Siam O. Lieu, Qiuyan Chen, Nan-qian Li, and A. Catharine Ross
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802
Running Title: Inflammation opposes retinoid induced CYP26 expression
Address for reprint requests and other correspondence: A. C. Ross Pennsylvania State University S-126 Henderson Building South University Park, PA 16802 Phone: (814) 865-4721; Fax: (814) 863-6103 Email:
[email protected]
Total word Count: 7147 words; 4 Figures
1 Copyright © 2006 by the American Physiological Society.
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Abstract
Retinoic acid (RA), a principal metabolite of vitamin A (retinol), is an essential endogenous regulator of gene transcription, and an important therapeutic agent. The catabolism of RA must be well regulated to maintain physiological concentrations of RA. The cytochrome P450 gene family, CYP26, which encodes retinoic acid-4-hydroxylase activity, is strongly implicated in the oxidation of RA. Inflammation alters the expression of numerous genes; however, whether inflammation affects CYP26 expression is not well understood. We have investigated the regulation of CYP26A1 and CYP26B1 mRNA levels by RA and lipopolysaccharide (LPS) in rat liver, as the liver is centrally involved in retinoid metabolism and the acute phase response to LPS. Both CYP26A1 and CYP26B1 mRNA were induced in b, P < 0.05. 0.061 represents a borderline significant difference between the RA and RA + LPS treated rats for aqueous-phase metabolites in liver.
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Fig. 4. Poly-I:C, as well as lipopolysaccharide (LPS), abrogates the response of CYP26A1 after its induction by retinoic acid (RA). Rats were treated with 500 ÂBg of RA or vehicle and then with LPS or poly-I:C (PIC) or vehicle 4 h later. A, CYP26A1 mRNA was detected by Northern blot analysis using poly(A)+-enriched RNA from pooled rat liver from each treatment group. B, Loading control, showing the ethidium bromide-stained agarose gel prior to transfer to the Nytran membrane for Northern blot analysis. C, RT-PCR amplification of rat liver RNA using 33P-dATP incorporation during PCR (see MATERIALS AND METHODS). RNA from n= 3-4 individual rats/group was subjected to PCR analysis. Bars show the mean ± SE. The insert shows results from one or two rats/group, visualized by X-ray film exposure of the polyacrylamide gel prior to cutting and counting the gel.
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