Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4
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<sub>2</sub> (PGE<sub>2</sub>) secreted by hAM-MSCs on neutrophil extracellula...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2831 |
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| author | Gibrán Alejandro Estúa-Acosta Beatriz Buentello-Volante Fátima Sofía Magaña-Guerrero José Eduardo-Aguayo Flores Oscar Vivanco-Rojas Ilse Castro-Salas Karla Zarco-Ávila Mariana A. García-Mejía Yonathan Garfias |
| author_facet | Gibrán Alejandro Estúa-Acosta Beatriz Buentello-Volante Fátima Sofía Magaña-Guerrero José Eduardo-Aguayo Flores Oscar Vivanco-Rojas Ilse Castro-Salas Karla Zarco-Ávila Mariana A. García-Mejía Yonathan Garfias |
| author_sort | Gibrán Alejandro Estúa-Acosta |
| collection | DOAJ |
| description | 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<sub>2</sub> (PGE<sub>2</sub>) secreted by hAM-MSCs on neutrophil extracellular trap (NET) release and to characterize the role of its receptors (EP2/EP4) in PAD-4 and NFκB 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<sub>2</sub> inhibitor MF-63, PGE<sub>2</sub>, EP2/EP4 agonists, and the selective PAD-4 inhibitor GSK-484. NET release, PAD-4, and NFκB 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<sub>2</sub> 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<sub>2</sub> and EP2/EP4 agonists and GSK-484 increased NFκB phosphorylation. Taken together, these results suggest that hAM-MSC exert their immunomodulatory activities through PGE<sub>2,</sub> 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. |
| first_indexed | 2024-03-10T00:27:12Z |
| format | Article |
| id | doaj.art-f39bec6bc89f4885b5861fd467168e22 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:27:12Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f39bec6bc89f4885b5861fd467168e222023-11-23T15:32:58ZengMDPI AGCells2073-44092022-09-011118283110.3390/cells11182831Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4Gibrán Alejandro Estúa-Acosta0Beatriz Buentello-Volante1Fátima Sofía Magaña-Guerrero2José Eduardo-Aguayo Flores3Oscar Vivanco-Rojas4Ilse Castro-Salas5Karla Zarco-Ávila6Mariana A. García-Mejía7Yonathan Garfias8Cell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoCell and Tissue Biology, Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City 06800, MexicoHuman 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<sub>2</sub> (PGE<sub>2</sub>) secreted by hAM-MSCs on neutrophil extracellular trap (NET) release and to characterize the role of its receptors (EP2/EP4) in PAD-4 and NFκB 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<sub>2</sub> inhibitor MF-63, PGE<sub>2</sub>, EP2/EP4 agonists, and the selective PAD-4 inhibitor GSK-484. NET release, PAD-4, and NFκB 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<sub>2</sub> 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<sub>2</sub> and EP2/EP4 agonists and GSK-484 increased NFκB phosphorylation. Taken together, these results suggest that hAM-MSC exert their immunomodulatory activities through PGE<sub>2,</sub> 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.https://www.mdpi.com/2073-4409/11/18/2831NETimmunomodulationprostaglandin E<sub>2</sub>amniotic membranemesenchymal stem cellsEP2 |
| spellingShingle | Gibrán Alejandro Estúa-Acosta Beatriz Buentello-Volante Fátima Sofía Magaña-Guerrero José Eduardo-Aguayo Flores Oscar Vivanco-Rojas Ilse Castro-Salas Karla Zarco-Ávila Mariana A. García-Mejía Yonathan Garfias Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 Cells NET immunomodulation prostaglandin E<sub>2</sub> amniotic membrane mesenchymal stem cells EP2 |
| title | Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 |
| title_full | Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 |
| title_fullStr | Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 |
| title_full_unstemmed | Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 |
| title_short | Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE<sub>2</sub> Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4 |
| title_sort | human amniotic membrane mesenchymal stem cell synthesized pge sub 2 sub exerts an immunomodulatory effect on neutrophil extracellular trap in a pad 4 dependent pathway through ep2 and ep4 |
| topic | NET immunomodulation prostaglandin E<sub>2</sub> amniotic membrane mesenchymal stem cells EP2 |
| url | https://www.mdpi.com/2073-4409/11/18/2831 |
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