Vitamin A status significantly alters nuclear factor-kappaB activity assessed by in vivo imaging.
Our study aimed to investigate, in vivo, the relationship between vitamin A status and NF-kappaB activity, a transcription factor central in regulating inflammatory and immune responses. We used a novel transgenic murine NF-kappaB-luciferase reporter model that enabled molecular imaging of NF-kappaB activity in live mice via an intensified image-capture apparatus. Whole-body luminescence, which reflects overall NF-kappaB activity, was elevated 2.2-fold in vitamin A-deficient (VAD) mice compared with control mice. Specifically, NF-kappaB activity in VAD mice was increased 1.8-fold in the lymph nodes and 1.4-fold in the thymus and, NF-kappaB induction in UVB radiation-exposed skin was also enhanced in VAD mice compared with control mice. The administration of all-trans retinoic acid to VAD mice resulted in a transient reduction in NF-kappaB activity and, conversely, a single dose of the RAR-pan-antagonist, AGN 194310, administered to control mice, led to a marked, transient induction of whole-body luminescence. Our results suggest that vitamin A status, and vitamin A itself, affects NF-kappaB activity in vivo and that the elevated NF-kappaB activity in VAD may be a mechanism underlying some of the features of VAD syndrome.
Austenaa
Liv M I
LM
Department of Nutrition, Faculty of Medicine, University of Oslo, Norway.
Carlsen
Harald
H
Ertesvag
Aase
A
Alexander
George
G
Blomhoff
Heidi K
HK
Blomhoff
Rune
R
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D017930:Genes, Reporter; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D013601:T-Lymphocytes / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014466:Ultraviolet Rays; D014802:Vitamin A Deficiency / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
C121616:4-((4-(4-ethylphenyl)-2,2-dimethyl-(2H)-thiochromen-6-yl)ethynyl)benzoic acid; D001565:Benzoates; D007145:Immunoglobulin kappa-Chains; D016328:NF-kappa B; D013876:Thiophenes; D014212:Tretinoin; D008156:Luciferases