Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine

Although the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated...

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Bibliographic Details
Published in:Scientific reports 2019-09, Vol.9 (1), p.13721-10, Article 13721
Main Authors: Branco, Anna Cláudia Calvielli Castelo, Pereira, Nátalli Zanete, Yoshikawa, Fábio Seiti Yamada, Oliveira, Luanda Mara da Silva, Teixeira, Franciane Mouradian Emidio, Oliveira, Luana de Mendonça, Pietrobon, Anna Julia, Torrealba, Marina Passos, de Lima, Josenilson Feitosa, Duarte, Alberto José da Silva, Sato, Maria Notomi
Format: Article
Language:English
Subjects:
Adult
Chemokine CCL2 - metabolism
Chemokines
Cord blood
CXCL10 protein
Down-Regulation - drug effects
Female
Fetal Blood - drug effects
Fetal Blood - metabolism
Gene regulation
Histamine
Histamine - pharmacology
Histamine receptors
Homeostasis
Humans
Imidazoles - pharmacology
Immunomodulation
Infant, Newborn
Inflammation
Inflammation - metabolism
Interferon-gamma - metabolism
Leukocytes (mononuclear)
Lipopolysaccharides
Lipopolysaccharides - pharmacology
Male
Monocyte chemoattractant protein 1
Monocytes
Monocytes - drug effects
Monocytes - metabolism
Neonates
NF-κB protein
Quinolines - pharmacology
Receptors, Histamine - metabolism
Signal Transduction - drug effects
TLR4 protein
Toll-Like Receptor 4 - agonists
Toll-like receptors
Transcription
γ-Interferon
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Summary:Although the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-γ-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-κB and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-50227-8