The short chain fatty acid sodium butyrate regulates the induction of CD1a in developing dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells with attributes for priming/activating T cells and mediating immune responses. Considering the importance of DCs in the initiation of immune responses, it will be of interest to study their mechanisms of regulation. Histone-modifying enzymes, such as histone deacetylases (HDACs), are critical in controlling chromatin organization. The aim of our study was to investigate DC differentiation under the influence of sodium butyrate (NaB), a short chain fatty acid that is a histone deacetylase inhibitor. Monocytes from healthy individuals were differentiated into immature DCs with IL-4 and GM-CSF in the presence or absence of NaB. DC differentiation was evaluated by CD14 and CD1a expression by flow cytometry. We observed that monocytes stimulated to differentiate in the presence of NaB displayed colony formation and dendritic cell morphology, lost CD14 and showed decreased secretion of IL-1β. The acquisition of CD1a, however, was impaired. Being a natural short chain fatty acid, NaB may regulate CD1a acquisition independently of its HDAC inhibitory activity. We observed that the addition of peroxisome proliferator-activated receptor γ (PPAR-γ) antagonist (GW9662) did not reverse NaB effect, suggesting this was not the pathway involved. On the other hand, CD1a can also be induced by toll like receptors 2 (TLR 2) agonists, such as Pam3Cys, and NaB inhibited this effect. Our data suggest that the histone deacetylase inhibitor NaB instead of impairing DC differentiation inhibits the acquisition of CD1a induced both by cytokines and by TLR 2 agonist stimulus. Furthermore, this occurs at the transcriptional level as NaB led to a decrease in mRNA levels of CD1a and upregulation of CD1d.
Nascimento
Clarissa Rodrigues
CR
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Freire-de-Lima
Célio G
CG
da Silva de Oliveira
Andréia
A
Rumjanek
Franklin D
FD
Rumjanek
Vivian M
VM
D000813:Anilides / Q000494:pharmacology; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D009000:Monocytes / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D018949:Antigens, CD1; D055610:Antigens, CD1d; D002087:Butyrates; C419393:CD1a antigen; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006655:Histone Deacetylases