Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-/M-CSF Signaling Axis in Human Monocytes

In recent years, the macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage CSF (GM-CSF) cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells...

Descripción completa

Detalles Bibliográficos
Autores: Rodríguez, Ramón M., Suárez Álvarez, Beatriz, Lavín, José L., Ascensión, Alex M., González, Monika, Lozano, Juan J., Raneros, Aroa B., Bulnes, Paula D., Vidal Castiñeira, Jose R., Huidobro Fernández, Covadonga|||0000-0001-9823-3846, Martín Martín, Cristina, Sanz, Ana B., Ruiz Ortega, Marta, Puig Kröger, Amaya, Corbí, Angel L., Araúzo Bravo, Marcos J., Aransay, Ana M., Lopez Larrea, Carlos|||0000-0001-9988-1730
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Oviedo (UNIOVI)
Repositorio:RUO. Repositorio Institucional de la Universidad de Oviedo
Idioma:inglés
OAI Identifier:oai:digibuo.uniovi.es:10651/71072
Acceso en línea:https://hdl.handle.net/10651/71072
https://dx.doi.org/10.1016/j.celrep.2019.09.035
Access Level:acceso abierto
Palabra clave:inflammatory response
transcriptional regulation
GM-/M-CSF
DNA methylation
chromatin
Descripción
Sumario:In recent years, the macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage CSF (GM-CSF) cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells integrate these signals. In order to understand the regulatory networks associated with the GM/M-CSF signaling axis, we analyzed DNA methylation in human monocytes. Our results indicate that GM-CSF induces activation of the inflammatory program and extensive DNA methylation changes, while M-CSF-polarized cells are in a less differentiated state. This inflammatory program is mediated via JAK2 associated with the GM-CSF receptor and the downstream extracellular signal-regulated (ERK) signaling. However, PI3K signaling is associated with a negative regulatory loop of the inflammatory program and M-CSF autocrine signaling in GMCSF- polarized monocytes. Our findings describe the regulatory networks associated with the GM/MCSF signaling axis and how they contribute to the establishment of the inflammatory program associated with monocyte activation.

Similares en LA Referencia