a1 Department of Nutritional Sciences, 110 Chandlee Laboratory, Pennsylvania State University, University Park, PA 16802, USA
a2 Department of Nutritional Sciences, Huck Institute for Life Science, Pennsylvania State University, University Park, PA 16802, USA
Vitamin A (VA) plays an important role in post-natal lung development and maturation. Previously, we have reported that a supplemental dose of VA combined with 10 % of all-trans-retinoic acid (VARA) synergistically increases retinol uptake and retinyl ester (RE) storage in neonatal rat lung, while up-regulating several retinoid homeostatic genes including lecithin:retinol acyltransferase (LRAT) and the retinol-binding protein receptor, stimulated by retinoic acid 6 (STRA6). However, whether inflammation has an impact on the expression of these genes and thus compromises the ability of VARA to increase lung RE content is not clear. Neonatal rats, 7- to 8-d-old, were treated with VARA either concurrently with lipopolysaccharide (LPS; Expt 1) or 12 h after LPS administration (Expt 2); in both studies, lung tissue was collected 6 h after VARA treatment, when RE formation is maximal. Inflammation was confirmed by increased IL-6 and chemokine (C–C motif) ligand 2 (CCL2) gene expression in lung at 6 h and C-reactive protein in plasma at 18 h. In both studies, LPS-induced inflammation only slightly reduced, but did not prevent the VARA-induced increase in lung RE. Quantitative RT-PCR showed that co-administration of LPS with VARA slightly attenuated the VARA-induced increase of LRAT mRNA, but not of STRA6 or cytochrome P450 26B1, the predominant RA hydroxylase in lung. By 18 h post-LPS, expression had subsided and none of these genes differed from the level in the control group. Overall, the present results suggest that retinoid homeostatic gene expression is reduced modestly, if at all, by acute LPS-induced inflammation and that VARA is still effective in increasing lung RE under conditions of moderate inflammation.
(Received May 21 2012)
(Revised June 29 2012)
(Accepted July 27 2012)
(Online publication September 05 2012)
Abbreviations: CCL2, chemokine (C–C motif) ligand 2; CRP, C-reactive protein; CYP26B1, cytochrome P450 26B1; LPS, lipopolysaccharide; LRAT, lecithin:retinol acyltransferase; RA, retinoic acid; RE, retinyl ester; STRA6, stimulated by retinoic acid 6; VA, vitamin A; VARA, supplemental dose of vitamin A combined with 10 % of all-trans-retinoic acid