NF-κB Drives the Synthesis of Melatonin in RAW 264.7 Macrophages by Inducing the Transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) Gene
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
05/11/2013
05/11/2013
2012
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Resumo |
We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-kappa B) induces the synthesis of melatonin by macrophages and that macrophage-synthesized melatonin modulates the function of these professional phagocytes in an autocrine manner. Expression of a DsRed2 fluorescent reporter driven by regions of the aa-nat promoter, that encodes the key enzyme involved in melatonin synthesis (arylalkylamine-N-acetyltransferase), containing one or two upstream kappa B binding sites in RAW 264.7 macrophage cell lines was repressed when NF-kappa B activity was inhibited by blocking its nuclear translocation or its DNA binding activity or by silencing the transcription of the RelA or c-Rel NF-kappa B subunits. Therefore, transcription of aa-nat driven by NF-kappa B dimers containing RelA or c-Rel subunits mediates pathogen-associated molecular patterns (PAMPs) or pro-inflammatory cytokine-induced melatonin synthesis in macrophages. Furthermore, melatonin acts in an autocrine manner to potentiate macrophage phagocytic activity, whereas luzindole, a competitive antagonist of melatonin receptors, decreases macrophage phagocytic activity. The opposing functions of NF-kappa B in the modulation of AA-NAT expression in pinealocytes and macrophages may represent the key mechanism for the switch in the source of melatonin from the pineal gland to immune-competent cells during the development of an inflammatory response. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [07/7871-6] Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) |
Identificador |
PLOS ONE, SAN FRANCISCO, v. 7, n. 12, supl. 4, Part 1-2, pp. 214-220, DEC 21, 2012 1932-6203 http://www.producao.usp.br/handle/BDPI/41908 10.1371/journal.pone.0052010 |
Idioma(s) |
eng |
Publicador |
PUBLIC LIBRARY SCIENCE SAN FRANCISCO |
Relação |
PLOS ONE |
Direitos |
openAccess Copyright PUBLIC LIBRARY SCIENCE |
Palavras-Chave | #PINEAL-GLAND #RESPONSE ELEMENT #C-REL #ACTIVATION #CELLS #EXPRESSION #RECEPTORS #ENDOCRINE #KB #INHIBITION #MULTIDISCIPLINARY SCIENCES |
Tipo |
article original article publishedVersion |