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Molecular Basis for Defining the Pineal Gland and Pinealocytes as Targets for Tumor Necrosis Factor

2011; Frontiers Media; Volume: 2; Linguagem: Inglês

10.3389/fendo.2011.00010

1664-2392

Claudia E. Carvalho‐Sousa, Sanseray da Silveira Cruz‐Machado, Eduardo Koji Tamura, Pedro Augusto Carlos Magno Fernandes, Luciana Pinato, Sandra Márcia Muxel, Erika Cecon, Regina P. Markus,

Immune Response and Inflammation

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.