Brief refeeding rapidly reverses dietary restriction-induced nuclear factor-kappaB downregulation in peritoneal resident cells.
BACKGROUND
Malnutrition impairs host immunity, resulting in high mortality and morbidity, secondary to infections. Nuclear factor kappaB (NFkappaB) plays a critical role in host defense, but how quickly refeeding normalizes the impaired NFkappaB activity in peritoneal resident cells (PRCs) is unknown. Our aim was to investigate the effects of 1-day ad libitum refeeding on severe diet restriction-induced NFkappaB activity in PRCs.


METHODS
Mice received chow, 146 g/kg per day (ad libitum) or 36.5 g/kg per day (severe diet restriction), for 7 days. One-half the mice in the diet-restricted group were then fed ad libitum for 1 day (refeeding). PRCs were harvested by peritoneal lavage. After incubation with tumor necrosis factor-alpha (TNF-alpha), nuclear translocation of NFkappaB in PRCs was investigated using laser scanning cytometry.


RESULTS
The main subpopulation of PRCs was macrophages in all groups. Mean fluorescence intensity over the nuclear area at 0 or 100 ng/mL of TNF-alpha was 16 +/- 2 or 31 +/- 8* in the ad libitum, 20 +/- 4 or 19 +/- 3 in the severe diet-restricted, and 20 +/- 4 or 30 +/- 5* in the refeeding group, respectively (*p < .05 versus 0 ng/mL of TNF-alpha in each group versus 100 ng/mL of TNF-alpha in diet-restricted group). Cytoplasmic accumulation of NFkappaB was significantly increased after TNF-alpha stimulation in the refed group but not in the ad libitum group.


CONCLUSIONS
The blunted NFkappaB activity in PRCs, after exposure to inflammatory stimuli, was restored after 1 day of refeeding, with increased accumulation of NFkappaB in the cytoplasm. Even brief nutritional replenishment in malnutrition may improve host defense by restoring NFkappaB activity and thereby improving macrophage functions.
Kang
Woodae
W
Surgical Center, University of Tokyo, Japan. kang-woodae@umin.ac.jp
Saito
Hideaki
H
Fukatsu
Kazuhiko
K
Nagawa
Hirokazu
H
Ikeda
Shigeo
S
D000818:Animals; D001835:Body Weight; D015536:Down-Regulation; D005502:Food; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D010537:Peritoneum / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha