Neuronal NF-kappaB influences thermoregulation and survival in a sepsis model.

Abstract

Gene regulation in sepsis is known to be controlled by the transcription factor NF-kappaB. However, the function of neuronal NF-kappaB in sepsis is not well defined. In a mouse model of sepsis induced by i.p. injection of lipopolysaccharides (LPS), we found an activation of NF-kappaB in the brain as shown by the induction of a transgenic NF-kappaB reporter. Inhibition of neuronal NF-kappaB by cell-specific expression of the NF-kappaB super-repressor IkappaBalpha-SR improved LPS-induced hypothermia and survival but had no effect on body weight or on the humoral response to LPS. In contrast, glial inhibition of NF-kappaB did not influence body temperature and survival. By immunohistochemistry, we detected the active NF-kappaB subunit RelA in neuronal nuclei of the organum vasculosum of the lamina terminalis. Our data reveal an important role of neuronal NF-kappaB in thermoregulation and survival. The upcoming group of NF-kappaB inhibitors may have a place in the treatment of the acute-phase response.

• Authors: Eric Jüttler, Ioana Inta, Verena Eigler, Oliver Herrmann, Ira Maegele, Christiane Maser-Gluth, Markus Schwaninger
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 189 Issue 1-2 Pg. 41-9 (Sep 2007) ISSN: 0165-5728 [Print] Netherlands
• PMID: 17655939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Glial Fibrillary Acidic Protein
• NF-kappa B
• Polysaccharides
• Phosphopyruvate Hydratase

Topics

• Animals
• Body Temperature (drug effects)
• Body Weight (drug effects)
• Brain (drug effects, pathology)
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Embryo, Mammalian
• Gene Expression Regulation (drug effects)
• Glial Fibrillary Acidic Protein (metabolism)
• Hypothermia (chemically induced, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NF-kappa B (genetics, physiology)
• Neural Inhibition (drug effects, physiology)
• Phosphopyruvate Hydratase (metabolism)
• Polysaccharides (adverse effects)
• Sepsis (chemically induced, mortality, pathology, physiopathology)
• Time Factors
• Transfection