Glia-Pinealocyte Network: The Paracrine Modulation of Melatonin Synthesis by Tumor Necrosis Factor (TNF)


Autoria(s): Cruz-Machado, Sanseray da Silveira; Pinato, Luciana; Tamura, Eduardo Koji; Sousa, Cláudia Emanuele Carvalho de; Markus, Regina Pekelmann
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

06/11/2013

06/11/2013

2012

Resumo

The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [07/07871-6]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Conselho Nacional de Pesquisa (CNPq)

Conselho Nacional de Pesquisa - CNPq [305378/2009-0]

Identificador

PLOS ONE, SAN FRANCISCO, v. 7, n. 7, supl. 2, Part 1-2, pp. 271-280, 37438, 2012

1932-6203

http://www.producao.usp.br/handle/BDPI/42085

10.1371/journal.pone.0040142

http://dx.doi.org/10.1371/journal.pone.0040142

Idioma(s)

eng

Publicador

PUBLIC LIBRARY SCIENCE

SAN FRANCISCO

Relação

PLOS ONE

Direitos

openAccess

Copyright PUBLIC LIBRARY SCIENCE

Palavras-Chave #NF-KAPPA-B #INNATE IMMUNE-RESPONSE #CELL-WALL COMPONENTS #TOLL-LIKE RECEPTOR-4 #GLAND #RAT #SYSTEM #LIPOPOLYSACCHARIDE #ACTIVATION #INCREASE #MULTIDISCIPLINARY SCIENCES
Tipo

article

original article

publishedVersion