title: Epigenetic Control of Macrophage Shape Transition towards an Atypical Elongated Phenotype by Histone Deacetylase Activity.
abstract: Inflammatory chronic pathologies are complex processes characterized by an imbalance between the resolution of the inflammatory phase and the establishment of tissue repair. The main players in these inflammatory pathologies are bone marrow derived monocytes (BMDMs). However, how monocyte differentiation is modulated to give rise to specific macrophage subpopulations (M1 or M2) that may either maintain the chronic inflammatory process or lead to wound healing is still unclear. Considering that inhibitors of Histone Deacetylase (HDAC) have an anti-inflammatory activity, we asked whether this enzyme would play a role on monocyte differentiation into M1 or M2 phenotype and in the cell shape transition that follows. We then induced murine bone marrow progenitors into monocyte/macrophage differentiation pathway using media containing GM-CSF and the HDAC blocker, Trichostatin A (TSA). We found that the pharmacological inhibition of HDAC activity led to a shape transition from the typical macrophage pancake-like shape into an elongated morphology, which was correlated to a mixed M1/M2 profile of cytokine and chemokine secretion. Our results present, for the first time, that HDAC activity acts as a regulator of macrophage differentiation in the absence of lymphocyte stimuli. We propose that HDAC activity down regulates macrophage plasticity favoring the pro-inflammatory phenotype.
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cabanel
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Brand
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Oliveira-Nunes
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariela Pires
authors.initials: MP
authors.lastname: Cabral-Piccin
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcela Freitas
authors.initials: MF
authors.lastname: Lopes
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Jose Marques
authors.initials: JM
authors.lastname: Brito
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe Leite
authors.initials: FL
authors.lastname: de Oliveira
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcia Cury
authors.initials: MC
authors.lastname: El-Cheikh
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Katia
authors.initials: K
authors.lastname: Carneiro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000737:chemistry; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology*; D009569:Nitric Oxide / Q000737:chemistry; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D006877:Hydroxamic Acids; D009569:Nitric Oxide; C012589:trichostatin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1