NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene

We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-κB) 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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e52010
Main Authors: Muxel, Sandra Marcia, Pires-Lapa, Marco Antonio, Monteiro, Alex Willian Arantes, Cecon, Erika, Tamura, Eduardo Koji, Floeter-Winter, Lucile Maria, Markus, Regina P
Format: Article
Language:English
Subjects:
Acetyltransferase
Animals
Arylalkylamine N-Acetyltransferase - genetics
Arylalkylamine N-Acetyltransferase - metabolism
Autocrine signalling
Binding sites
Biology
Cell Line
Cell lines
Cell Nucleolus - metabolism
Chemical synthesis
Deoxyribonucleic acid
Dimers
DNA
DNA methylation
Dose-Response Relationship, Drug
Endocrine system
Enzymes
Fluorescence
Gene Expression Regulation - drug effects
Gene silencing
Genes
Inflammation
Inflammatory response
Lipopolysaccharides - pharmacology
Macrophages
Macrophages - drug effects
Macrophages - immunology
Macrophages - metabolism
Medicine
Melatonin
Melatonin - biosynthesis
Melatonin receptors
Mice
N-Acetyltransferase
NF-kappa B - metabolism
NF-κB protein
Nuclear transport
Paracrine Communication
Phagocytes
Phagocytosis - immunology
Physiology
Pineal gland
Plasmids
Promoter Regions, Genetic
Prostate cancer
Protein Transport
Proteins
Receptors
RelA protein
Response Elements
Rodents
Transcription, Genetic - drug effects
Transcriptional Activation - drug effects
Translocation
Zymosan - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-κB) 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 κB binding sites in RAW 264.7 macrophage cell lines was repressed when NF-κB 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-κB subunits. Therefore, transcription of aa-nat driven by NF-κB 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-κB 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0052010