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

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Calvielli Castelo Branco, Anna Claudia ^{[1, 2]} ; Pereira, Natalli Zanete ^[2] ; Yamada Yoshikawa, Fabio Seiti ^[2] ; da Silva Oliveira, Luanda Mara ^[2] ; Emidio Teixeira, Franciane Mouradian ^{[1, 2]} ; Oliveira, Luana de Mendonca ^[2] ; Pietrobon, Anna Julia ^{[1, 2]} ; Torrealba, Marina Passos ^[2] ; de Lima, Josenilson Feitosa ^[2] ; da Silva Duarte, Alberto Jose ^[2] ; Sato, Maria Notomi ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Trop Med Inst Sao Paulo, Dept Dermatol, Lab Med Invest, LIM 56, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, SEP 23 2019.
• Citações Web of Science: 0

Resumo

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-gamma-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-kappa B 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. (AU)

• Processo FAPESP: 16/24680-9 - Avaliação da inflamação de trofoblastos vilosos humanos na infecção por Zika e dengue vírus
• Beneficiário: Anna Cláudia Calvielli Castelo Branco
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/16524-6 - Efeito da histamina na ativação de células dendríticas e células TCD4+ mediado por agonistas de receptores toll-like em recém-natos
• Beneficiário: Maria Notomi Sato
• Modalidade de apoio: Auxílio à Pesquisa - Regular