Neuronal NF-kappaB influences thermoregulation and survival in a sepsis model.
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.
Jüttler
Eric
E
Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
Inta
Ioana
I
Eigler
Verena
V
Herrmann
Oliver
O
Maegele
Ira
I
Maser-Gluth
Christiane
C
Schwaninger
Markus
M
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011134:Polysaccharides / Q000009:adverse effects; D018805:Sepsis / Q000139:chemically induced / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014162:Transfection
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D011134:Polysaccharides; D010751:Phosphopyruvate Hydratase