The RelA/cRel nuclear factor-B (NF-B) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages

Autor(es)

Muxel, Sandra Marcia ^[1] ; Laranjeira-Silva, Maria Fernanda ^[1] ; Carvalho-Sousa, Claudia Emanuelle ^[1] ; Floeter-Winter, Lucile Maria ^[1] ; Markus, Regina P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Fisiol, Inst Biociencias, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pineal Research; v. 60, n. 4, p. 394-404, MAY 2016.
• Citações Web of Science: 22

Resumo

Lipopolysaccharide (LPS) modulates the transcription of the gene that codifies the enzyme arylalkylamine-N-acetyltransferase (AA-NAT) through nuclear translocation of the transcription factor nuclear factor--light-chain-enhancer of activated B cells (NF-B). AA-NAT converts serotonin to N-acetylserotonin, the ultimate precursor of melatonin. Activation of kappa B elements (aa-nat-B), localized in the promoter (nat-B1 and nat-B2), leads to Aa-nat transcription in RAW 264.7 macrophages. Competitive electrophoretic mobility shift assay (EMSA) with oligonucleotide probes corresponding to each of the two elements, as well as a NF-B consensus corresponding probe, revealed different specificities for each B element. In addition, activator protein-1 (AP-1) as well as signal transducers and activator of transcription-1 and 3 (STAT-1; STAT-3) competed with NF-B for binding to nat-B1, while only STAT-3 competed with NF-B for binding to nat-B2. According to co-immunoprecipitation (ChiP) assays, these two sites are able to distinguish NF-B subunits. The sequence nat-B1 bound dimers containing p52, RelA, and cRel, while nat-B2 bound preferentially p50, p52, and RelA, and did not bind cRel. The expression of RelA and cRel is essential for the induction of Aa-nat expression and melatonin synthesis. Considering that the expression of cRel is induced by the earlier expressed p50/RelA, the differential effects of NF-B dimers may be intimately associated with the temporal regulation of inflammatory responses, with the resolution phase being associated with paracrine and autocrine melatonin effects. Such data suggest that the proven effects of exogenous melatonin in the resolution phase of inflammation are paralleled by the effects of locally synthesized melatonin in immune cells. (AU)

• Processo FAPESP: 14/50717-1 - Estudos bioquímicos, moleculares e funcionais da relação Leishmania-macrófago
• Beneficiário: Lucile Maria Floeter-Winter
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/52688-8 - Bioquímica, fisiologia e genômica funcional da relação Leishmania-macrófago
• Beneficiário: Lucile Maria Floeter-Winter
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
• Beneficiário: Regina Pekelmann Markus
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/15263-4 - Alterações na composição de microRNAs em macrófagos infectados por Leishmania amazonensis
• Beneficiário: Sandra Marcia Muxel
• Modalidade de apoio: Auxílio à Pesquisa - Regular