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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Muxel, Sandra Marcia [1] ; Laranjeira-Silva, Maria Fernanda [1] ; Carvalho-Sousa, Claudia Emanuelle [1] ; Floeter-Winter, Lucile Maria [1] ; Markus, Regina P. [1]
Total Authors: 5
[1] Univ Sao Paulo, Dept Fisiol, Inst Biociencias, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Pineal Research; v. 60, n. 4, p. 394-404, MAY 2016.
Web of Science Citations: 22

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)

FAPESP's process: 12/15263-4 - Alterations in the composition of microRNAs in macrophages infected by Leishmania amazonensis
Grantee:Sandra Marcia Muxel
Support type: Regular Research Grants
FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
Grantee:Regina Pekelmann Markus
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/50717-1 - Biochemical, physiological and functional genomic studies of Leishmania-macrophage interaction
Grantee:Lucile Maria Floeter-Winter
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/52688-8 - Biochemical, physiological and functional genomics studies of Leishmania-macrophage interaction
Grantee:Lucile Maria Floeter-Winter
Support type: Research Projects - Thematic Grants