Artigo Acesso aberto Revisado por pares

Activin A skews macrophage polarization by promoting a proinflammatory phenotype and inhibiting the acquisition of anti-inflammatory macrophage markers

2011; Elsevier BV; Volume: 117; Issue: 19 Linguagem: Inglês

10.1182/blood-2010-09-306993

ISSN

1528-0020

Autores

Elena Sierra‐Filardi, Amaya Puig‐Kröger, Francisco J. Blanco, Concha Nieto, Rafael Bragado, María Isabel Palomero, Carmelo Bernabéu, Miguel A. Vega, Ángel L. Corbí,

Tópico(s)

Epigenetics and DNA Methylation

Resumo

Abstract M-CSF favors the generation of folate receptor β–positive (FRβ+), IL-10–producing, immunosuppressive, M2-polarized macrophages [M2 (M-CSF)], whereas GM-CSF promotes a proinflammatory, M1-polarized phenotype [M1 (GM-CSF)]. In the present study, we found that activin A was preferentially released by M1 (GM-CSF) macrophages, impaired the acquisition of FRβ and other M2 (M-CSF)–specific markers, down-modulated the LPS-induced release of IL-10, and mediated the tumor cell growth–inhibitory activity of M1 (GM-CSF) macrophages, in which Smad2/3 is constitutively phosphorylated. The contribution of activin A to M1 (GM-CSF) macrophage polarization was evidenced by the capacity of a blocking anti–activin A antibody to reduce M1 (GM-CSF) polarization markers expression while enhancing FRβ and other M2 (M-CSF) markers mRNA levels. Moreover, an inhibitor of activin receptor-like kinase 4/5/7 (ALK4/5/7 or SB431542) promoted M2 (M-CSF) marker expression but limited the acquisition of M1 (GM-CSF) polarization markers, suggesting a role for Smad2/3 activation in macrophage polarization. In agreement with these results, expression of activin A and M2 (M-CSF)–specific markers was oppositely regulated by tumor ascites. Therefore, activin A contributes to the proinflammatory macrophage polarization triggered by GM-CSF and limits the acquisition of the anti-inflammatory phenotype in a Smad2-dependent manner. Our results demonstrate that activin A–initiated Smad signaling skews macrophage polarization toward the acquisition of a proinflammatory phenotype.

Referência(s)
Altmetric
PlumX