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α-Tocopherol Transfer Protein-Null Mice with Very Low α-Tocopherol Status Do Not Have an Enhanced
Megumi Hashida1, Katherine M Ranard2, Andrew J Steelman1,3
1Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Background:
The α-tocopherol transfer protein-null (Ttpa) mouse model is a valuable tool for studying the molecular and functional consequences of vitamin E (α-tocopherol, αT) deficiency. Because αT has been associated with reduced oxidative stress and improved immune function, we hypothesized that depleted αT concentration would exacerbate LPS-induced acute inflammatory response in the brain and heart of Ttpa mice fed a vitamin E deficient (VED) diet.
Objectives:
The objective was to investigate how extremely low αT status, followed by exposure to LPS, altered the acute inflammatory response to LPS in Ttpa and wild-type (Ttpa) mice.
Methods:
Three-week-old male Ttpa and Ttpa littermates (n = 36/genotype) ingested a VED diet ad libitum for 4 wk. At week 7, mice received an intraperitoneal LPS (1 or 10 μg/mouse) or saline (control) injection and were killed 4 h postinjection. Brain and heart IL-6 protein concentrations and tissue and serum αT concentrations were measured via ELISA and HPLC with photodiode array detection, respectively. Hippocampal Il-6, Tnf, and Gpx1 gene expression were measured via reverse transcriptase-quantitative polymerase chain reaction, and blood immune cell profiles were measured via a hematology analyzer.
Results:
αT accumulation in analyzed tissues and serum of Ttpa mice was substantially lower than Ttpa mice. Circulating white blood cell concentration, particularly lymphocytes, were lower in all LPS groups compared with controls (P < 0.01). The 10 μg LPS groups had elevated IL-6 in the cerebellum and heart compared with controls, confirming an acute inflammatory response (P < 0.01). Hippocampal and heart Il-6 gene expression in the LPS-treated Ttpa mice was upregulated in a dose-dependent manner (P < 0.05).
Conclusions:
The 10 μg LPS dose enhanced inflammatory markers in the brain, heart, and serum in each genotype but the lower αT status in Ttpa mice did not further impact the acute immune responses.
