, Volume 67, Issue 12, pp 2039-2056,
Open Access This content is freely available online to anyone, anywhere at any time.

Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene

Abstract

Beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 −/−) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1 +/+) mice efficiently cleave BC. Bcmo1 / mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1 / mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1 / mice and Bcmo1 +/+ mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1 / mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1 / mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 −/− mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.