Molecular imaging of the transcription factor NF-κB, a primary regulator of stress response

Harald Carlsen, George Alexander, Liv M I Austenaa, Kanae Ebihara, Rune Blomhoff

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

A wide range of environmental stress and human disorders involves inappropriate regulation of NF-κB, including cancers and numerous inflammatory conditions. We have developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time non-invasive imaging of NF-κB activity in intact animals. We show that, in the absence of stimulation, strong, intrinsic luminescence is evident in lymph nodes in the neck region, thymus, and Peyer's patches. Treating mice with stressors, such as TNF-α, IL-1α, or lipopolysaccharide (LPS) increases the luminescence in a tissue-specific manner, with the strongest activity observable in the skin, lungs, spleen, Peyer's patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue exhibit less intense activities. Exposure of the skin to a low dose of UV-B radiation increases luminescence in the exposed areas. In ocular experiments, LPS- and TNF-α injected NF-κB-luciferase transgenic mice exhibit a 20-40-fold increase in lens NF-κB activity, similar to other LPS- and TNF-α-responsive organs. Peak NF-κB activity occurs 6 h after injection of TNF-α and 12 h after injection of LPS. Peak activities occur, respectively, 3 and 6 h later than that in other tissues. Mice exposed to 360 J/m2 of UV-B exhibit a 16-fold increase in NF-κB activity 6 h after exposure, characteristically similar to TNF-α-exposed mice. Thus, in NF-κB-luciferase transgenic mice, NF-κB activity also occurs in lens epithelial tissue and is activated when the intact mouse is exposed to classical stressors. Furthermore, as revealed by real-time non-invasive imaging, induction of chronic inflammation resembling rheumatoid arthritis produces strong NF-κB activity in the affected joints. Finally, we have used the model to demonstrate NF-κB regulation by manipulating the Vitamin A status in mice. NF-κB activity is elevated in mice fed a Vitamin A deficient (VAD) diet, and suppressed by surplus doses of retinoic acid (RA). We thus demonstrate the development and use of a versatile model for monitoring NF-κB activation both in tissue homogenates and in intact animals after the use of classical activators, during disease progression and after dietary intervention.

Original languageEnglish
Pages (from-to)199-211
Number of pages13
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume551
Issue number1-2
DOIs
Publication statusPublished - Jul 13 2004

Fingerprint

Molecular Imaging
Transcription Factors
Lipopolysaccharides
Luminescence
Luciferases
Transgenic Mice
Peyer's Patches
Vitamin A
Lenses
Skin
Injections
Tretinoin
Interleukin-1
Thymus Gland
Small Intestine
Disease Progression
Adipose Tissue
Rheumatoid Arthritis
Myocardium
Neck

Keywords

  • Luciferase
  • Molecular imaging
  • NF-κB
  • Transgenic reporter mice
  • Vitamin A

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Molecular imaging of the transcription factor NF-κB, a primary regulator of stress response. / Carlsen, Harald; Alexander, George; Austenaa, Liv M I; Ebihara, Kanae; Blomhoff, Rune.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 551, No. 1-2, 13.07.2004, p. 199-211.

Research output: Contribution to journalArticle

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