Frontiers in Endocrinology (May 2011)

Molecular basis for defining pineal gland and pinealocytes as targets for tumor necrosis factor (TNF)

  • Cláudia Emanuele Carvalho-Sousa,
  • Sanseray eda Silveira Cruz-Machado,
  • Eduardo Koji Tamura,
  • Pedro A C. M. Fernandes,
  • Luciana ePinato,
  • Sandra M Muxel,
  • Erika eCecon,
  • Regina P. Markus

DOI
https://doi.org/10.3389/fendo.2011.00010
Journal volume & issue
Vol. 2

Abstract

Read online

The pineal gland, which is the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melatonin synthesis (arylalkylamine-N-acetyltransferase-alkyl-N-acetyltransferase, Aa-nat). Here we show that TNF receptors of the subtype 1 (TNF-R1) are expressed by astrocytes, microglia and pinealocytes. We also show that the activation of TNF triggers the nuclear factor kappa B (NFKB) pathway in pinealocytes by reducing the cytoplasmic level of the inhibitory nuclear factor kappa B protein of the subtype A (NFKBIA). The TNF-induced nuclear translocation of the p50/p50 NFKB transcription factor lacks a transactivation domain, and this phenomenon explains how TNF blocks the transcription of Aa-nat. In addition, the p65/RelA nuclear translocation was read-out following the expression of inducible nitric oxide synthase (iNOS) and the synthesis of nitric oxide NO. The increase in the transcription of genes activated by NFKB opens a new perspective for understanding the implication of the pineal gland in pathophysiological conditions.

Keywords