Contribution of TNF-alpha and nuclear factor-kappaB signaling to type 2 iodothyronine deiodinase activation in the mediobasal hypothalamus after lipopolysaccharide administration

Sanchez, E; Singru, PS; Wittmann, G [Wittmann, Gábor (Endokrin neurobio...), author] Laboratory of Endocrine Neurobiology (IEM / DEN); Nouriel, SS; Barrett, P; Fekete, C [Fekete, Csaba (Neuroendokrinológia), author] Laboratory of Integrative Neuroendocrinology (IEM / DEN); Lechan, RM ✉

English Article (Journal Article) Scientific
Published: ENDOCRINOLOGY 0013-7227 1945-7170 151 (8) pp. 3827-3835 2010
  • SJR Scopus - Endocrinology: D1
Identifiers
Subjects:
  • Biological sciences
  • Clinical medicine
To determine whether signaling through TNF and/or nuclear factor-kappaB contributes to bacterial lipopolysaccharide (LPS)-induced activation of type 2 iodothyronine deiodinase (D2) in tanycytes lining the floor and infralateral walls of the third ventricle, the effect of a TNF antagonist on D2 gene expression and LPS-induced Ikappa-Balpha expression in tanycytes were studied. Animals treated with soluble, rat, polyethylene glycol-conjugated TNF receptor type 1 (4 mg/kg body weight) before a single ip injection of LPS showed a significant reduction in circulating IL-6 levels but no effect on LPS-induced D2 mRNA in the majority of tanycytes with the exception of a subpopulation of alpha tanycytes in the wall of the third ventricle. LPS induced a rapid increase in Ikappa-Balpha mRNA in the pars tuberalis and a delayed response in alpha tanycytes but absent in all other tanycyte subsets. The LPS-induced increase in Ikappa-Balpha in the pars tuberalis was associated with increased TSHbeta gene expression in this tissue, but cAMP response element-binding protein (CREB) phosphorylation was observed only in a subset of alpha tanycytes. These data suggest that TNF and nuclear factor-kappaB signaling are not the primary, initiating mechanisms mediating the LPS-induced D2 response in tanycytes, but may contribute in part to sustaining the LPS-induced D2 response in a subset of alpha tanycytes. We hypothesize that in addition to TSH, other factors derived from the pars tuberalis may contribute to LPS-induced D2 activation in tanycytes.
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2025-02-25 06:06