NF kappa B Signaling Is Essential for the Lipopolysaccharide-Induced Increase of Type 2 Deiodinase in Tanycytes

E. M. de Vries, J. Kwakkel, L. Eggels, A. Kalsbeek, P. Barrett, E. Fliers, A. Boelen*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The enzyme type 2 deiodinase (D2) is a major determinant of T-3 production in the central nervous system. It is highly expressed in tanycytes, a specialized cell type lining the wall of the third ventricle. During acute inflammation, the expression of D2 in tanycytes is up-regulated by a mechanism that is poorly understood at present, but we hypothesized that cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit of NF kappa B) inflammatory signal transduction pathways are involved. In a mouse model for acute inflammation, we studied the effects of lipopolysaccharide (LPS) on mRNA expression of D2, JNK1, and RelA in the periventricular area (PE) and the arcuate nucleus-median eminence of the hypothalamus. We next investigated LPS-induced D2 expression in primary tanycyte cell cultures. In the PE, the expression of D2 was increased by LPS. In the arcuate nucleus, but not in the PE, we found increased RelA mRNA expression. Likewise, LPS increased D2 and RelA mRNA expression in primary tanycyte cell cultures, whereas JNK1 mRNA expression did not change. Phosphorylation of RelA and JNK1 was increased in tanycyte cell cultures 15-60 minutes after LPS stimulation, confirming activation of these pathways. Finally, inhibition of RelA with the chemical inhibitors sulfasalazine and 4-Methyl-N-1-(3-phenylpropyl)benzene-1,2-diamine (JSH-23) in tanycyte cell cultures prevented the LPS-induced-D2 increase. We conclude that NF kappa B signaling is essential for the up-regulation of D2 in tanycytes during inflammation.

Original languageEnglish
Pages (from-to)2000-2008
Number of pages9
JournalEndocrinology
Volume155
Issue number5
Early online date17 Mar 2014
DOIs
Publication statusPublished - 2014

Keywords

  • thyroid-hormone metabolism
  • messenger-ribonucleic-acid
  • sick euthyroid syndrome
  • iodothyronine deiodinase
  • mediobasal hypothalamus
  • bacterial lipopolysaccharide
  • nonthyroidal illness
  • rat hypothalamus
  • gene-expression
  • activation

Cite this

NF kappa B Signaling Is Essential for the Lipopolysaccharide-Induced Increase of Type 2 Deiodinase in Tanycytes. / de Vries, E. M.; Kwakkel, J.; Eggels, L.; Kalsbeek, A.; Barrett, P.; Fliers, E.; Boelen, A.

In: Endocrinology, Vol. 155, No. 5, 2014, p. 2000-2008.

Research output: Contribution to journalArticle

de Vries, EM, Kwakkel, J, Eggels, L, Kalsbeek, A, Barrett, P, Fliers, E & Boelen, A 2014, 'NF kappa B Signaling Is Essential for the Lipopolysaccharide-Induced Increase of Type 2 Deiodinase in Tanycytes', Endocrinology, vol. 155, no. 5, pp. 2000-2008. https://doi.org/10.1210/en.2013-2018
de Vries, E. M. ; Kwakkel, J. ; Eggels, L. ; Kalsbeek, A. ; Barrett, P. ; Fliers, E. ; Boelen, A. / NF kappa B Signaling Is Essential for the Lipopolysaccharide-Induced Increase of Type 2 Deiodinase in Tanycytes. In: Endocrinology. 2014 ; Vol. 155, No. 5. pp. 2000-2008.
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abstract = "The enzyme type 2 deiodinase (D2) is a major determinant of T-3 production in the central nervous system. It is highly expressed in tanycytes, a specialized cell type lining the wall of the third ventricle. During acute inflammation, the expression of D2 in tanycytes is up-regulated by a mechanism that is poorly understood at present, but we hypothesized that cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit of NF kappa B) inflammatory signal transduction pathways are involved. In a mouse model for acute inflammation, we studied the effects of lipopolysaccharide (LPS) on mRNA expression of D2, JNK1, and RelA in the periventricular area (PE) and the arcuate nucleus-median eminence of the hypothalamus. We next investigated LPS-induced D2 expression in primary tanycyte cell cultures. In the PE, the expression of D2 was increased by LPS. In the arcuate nucleus, but not in the PE, we found increased RelA mRNA expression. Likewise, LPS increased D2 and RelA mRNA expression in primary tanycyte cell cultures, whereas JNK1 mRNA expression did not change. Phosphorylation of RelA and JNK1 was increased in tanycyte cell cultures 15-60 minutes after LPS stimulation, confirming activation of these pathways. Finally, inhibition of RelA with the chemical inhibitors sulfasalazine and 4-Methyl-N-1-(3-phenylpropyl)benzene-1,2-diamine (JSH-23) in tanycyte cell cultures prevented the LPS-induced-D2 increase. We conclude that NF kappa B signaling is essential for the up-regulation of D2 in tanycytes during inflammation.",
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T1 - NF kappa B Signaling Is Essential for the Lipopolysaccharide-Induced Increase of Type 2 Deiodinase in Tanycytes

AU - de Vries, E. M.

AU - Kwakkel, J.

AU - Eggels, L.

AU - Kalsbeek, A.

AU - Barrett, P.

AU - Fliers, E.

AU - Boelen, A.

PY - 2014

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N2 - The enzyme type 2 deiodinase (D2) is a major determinant of T-3 production in the central nervous system. It is highly expressed in tanycytes, a specialized cell type lining the wall of the third ventricle. During acute inflammation, the expression of D2 in tanycytes is up-regulated by a mechanism that is poorly understood at present, but we hypothesized that cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit of NF kappa B) inflammatory signal transduction pathways are involved. In a mouse model for acute inflammation, we studied the effects of lipopolysaccharide (LPS) on mRNA expression of D2, JNK1, and RelA in the periventricular area (PE) and the arcuate nucleus-median eminence of the hypothalamus. We next investigated LPS-induced D2 expression in primary tanycyte cell cultures. In the PE, the expression of D2 was increased by LPS. In the arcuate nucleus, but not in the PE, we found increased RelA mRNA expression. Likewise, LPS increased D2 and RelA mRNA expression in primary tanycyte cell cultures, whereas JNK1 mRNA expression did not change. Phosphorylation of RelA and JNK1 was increased in tanycyte cell cultures 15-60 minutes after LPS stimulation, confirming activation of these pathways. Finally, inhibition of RelA with the chemical inhibitors sulfasalazine and 4-Methyl-N-1-(3-phenylpropyl)benzene-1,2-diamine (JSH-23) in tanycyte cell cultures prevented the LPS-induced-D2 increase. We conclude that NF kappa B signaling is essential for the up-regulation of D2 in tanycytes during inflammation.

AB - The enzyme type 2 deiodinase (D2) is a major determinant of T-3 production in the central nervous system. It is highly expressed in tanycytes, a specialized cell type lining the wall of the third ventricle. During acute inflammation, the expression of D2 in tanycytes is up-regulated by a mechanism that is poorly understood at present, but we hypothesized that cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit of NF kappa B) inflammatory signal transduction pathways are involved. In a mouse model for acute inflammation, we studied the effects of lipopolysaccharide (LPS) on mRNA expression of D2, JNK1, and RelA in the periventricular area (PE) and the arcuate nucleus-median eminence of the hypothalamus. We next investigated LPS-induced D2 expression in primary tanycyte cell cultures. In the PE, the expression of D2 was increased by LPS. In the arcuate nucleus, but not in the PE, we found increased RelA mRNA expression. Likewise, LPS increased D2 and RelA mRNA expression in primary tanycyte cell cultures, whereas JNK1 mRNA expression did not change. Phosphorylation of RelA and JNK1 was increased in tanycyte cell cultures 15-60 minutes after LPS stimulation, confirming activation of these pathways. Finally, inhibition of RelA with the chemical inhibitors sulfasalazine and 4-Methyl-N-1-(3-phenylpropyl)benzene-1,2-diamine (JSH-23) in tanycyte cell cultures prevented the LPS-induced-D2 increase. We conclude that NF kappa B signaling is essential for the up-regulation of D2 in tanycytes during inflammation.

KW - thyroid-hormone metabolism

KW - messenger-ribonucleic-acid

KW - sick euthyroid syndrome

KW - iodothyronine deiodinase

KW - mediobasal hypothalamus

KW - bacterial lipopolysaccharide

KW - nonthyroidal illness

KW - rat hypothalamus

KW - gene-expression

KW - activation

U2 - 10.1210/en.2013-2018

DO - 10.1210/en.2013-2018

M3 - Article

VL - 155

SP - 2000

EP - 2008

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 5

ER -