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