Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE(2) Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4
Por:
Alejandro Estua-Acosta, Gibran, Buentello-Volante, Beatriz, Sofia Magana-Guerrero, Fatima, Eduardo-Aguayo Flores, Jose, Vivanco-Rojas, Oscar, Castro-Salas, Ilse, Zarco-Avila, Karla, Garcia-Mejia, Mariana A., Garfias, Yonathan
Publicada:
1 sep 2022
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
Human amniotic membrane mesenchymal stem cells (hAM-MSC) secrete a
myriad of components with immunosuppressive activities. In the present
research, we aimed to describe the effect of prostaglandin E-2 (PGE(2))
secreted by hAM-MSCs on neutrophil extracellular trap (NET) release and
to characterize the role of its receptors (EP2/EP4) in PAD-4 and NF
kappa B activity in neutrophils. Human peripheral blood neutrophils were
ionomycin-stimulated in the presence of hAM-MSC conditioned medium (CM)
treated or not with the selective PGE(2) inhibitor MF-63, PGE(2),
EP2/EP4 agonists, and the selective PAD-4 inhibitor GSK-484. NET
release, PAD-4, and NF kappa B activation were analyzed. Ionomycin
induced NET release, which was inhibited in the presence of hAM-MSC-CM,
while CM from hAM-MSCs treated with MF-63 prevented NET release
inhibition. PGE(2) and EP2/EP4 agonists, and GSK-484 inhibited NET
release. EP2/EP4 agonists and GSK-484 inhibited H3-citrullination but
did not affect PAD-4 protein expression. Finally, PGE(2) and EP2/EP4
agonists and GSK-484 increased NF kappa B phosphorylation. Taken
together, these results suggest that hAM-MSC exert their
immunomodulatory activities through PGE(2,) inhibiting NET release in a
PAD-4-dependent pathway. This research proposes a new mechanism by which
hAM-MSC exert their activities when modulating the innate immune
response and inhibiting NET release.
Filiaciones:
Alejandro Estua-Acosta, Gibran:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Buentello-Volante, Beatriz:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Sofia Magana-Guerrero, Fatima:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Eduardo-Aguayo Flores, Jose:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Vivanco-Rojas, Oscar:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Castro-Salas, Ilse:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Zarco-Avila, Karla:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Garcia-Mejia, Mariana A.:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Garfias, Yonathan:
Inst Ophthalmol Conde Valenciana, Res Unit, Cell & Tissue Biol, Mexico City 06800, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Dept Biochem, Mexico City 04510, DF, Mexico
Green Published, gold
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