Strong in vivo activation of NF-kappaB in mouse lenses by classic stressors

Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2683-8. doi: 10.1167/iovs.02-0829.

Abstract

Purpose: To examine the in vivo activation of nuclear factor (NF)-kappaB in mouse lens epithelia by using bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, and UV-B radiation.

Methods: Transgenic mice containing the NF-kappaB-luciferase reporter were injected with LPS, TNF-alpha or, exposed to UV-B. After various exposure times, the mice were killed, and ocular, liver, lung, kidney, spleen, and skin tissue were obtained. Tissue homogenates were examined for luciferase activity with a luminometer. Groups of mice were also imaged in vivo through a light-intensified camera system to assess NF-kappaB activity.

Results: LPS- and TNF-alpha injected NF-kappaB-luciferase transgenic mice yielded 20- to 40-fold increases in lens NF-kappaB activity, similar to other LPS- and TNF-alpha-responsive organs. Peak NF-kappaB activity occurred 6 hours after injection of TNF-alpha and 12 hours after injection of LPS. Peak activities were, respectively, 3 and 6 hours later than that in other tissues. Mice exposed to 360 J/m(2) of UV-B exhibited a 16-fold increase in NF-kappaB activity 6 hours after exposure, which are characteristics similar to TNF-alpha-exposed mice. In vivo imaging of transgenic mice exposed to LPS, TNF-alpha, and UV-B radiation demonstrated a similarity between in vitro and in vivo measurements of NF-kappaB activity.

Conclusions: In NF-kappaB-luciferase transgenic mice, NF-kappaB activity occurs in lens epithelial tissue and is activated when the intact mouse is exposed to bacterial LPS, TNF-alpha, or UV-B. Lens epithelial NF-kappaB kinetics were comparable to those of other tissues, indicating that NF-kappaB may play a role in progression or arrest of lens disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Escherichia coli*
  • Female
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / radiation effects*
  • Lipopolysaccharides / pharmacology*
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • NF-kappa B / metabolism*
  • Oxidative Stress
  • Skin / metabolism
  • Skin / radiation effects
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Ultraviolet Rays

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Luciferases