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4. Embryo Quality Conditions the Secretory Profile of Tolerogenic Dendritic Cell DC‐10 During the Peri‐Implantation Period.

Author

Gori, Soledad, Fernández, Laura, Soczewski, Elizabeth, Schafir, Ana, Castagnola, Lara, Grasso, Esteban, Martínez, Gustavo, Leirós, Claudia Pérez, and Ramhorst, Rosanna

Subjects
EMBRYO implantation, MYELOID cells, DENDRITIC cells, STROMAL cells, MEDROXYPROGESTERONE
Abstract

Problem: The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)‐10 profile, a DC subset with high IL‐10 production. Since the implantation process implies an embryo‐endometrium‐immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality. Method of Study: Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl‐cAMP (Dec) was stimulated with human embryo‐conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group). Monocytes isolated from six healthy women were differentiated to DCs with rhGM‐CSF+rhIL‐4 in the presence/absence of conditioned media (CM) from decidualized cells stimulated with ECM or nontreated. Results: We found that decidualized cells stimulated with ECM sustain a myeloid regulatory cell profile on monocyte‐derived culture with increased frequency of CD1a‐CD14+ and CD83+CD86low cells. ND‐Dec sustained the higher expression of the DC‐10 markers, HLA‐G and IL‐10 whereas ID‐Dec diminished IL‐10 production (ID‐Dec: 135 ± 37.4 vs. Dec: 223.3 ± 49.9 pg/mL, p < 0.05). The treatment with ECM‐Dec sustained a higher IL‐10 production and prevented the increase of CD83/CD86 after LPS challenge regardless of embryo quality. Notably, TNF‐α production increased in ID‐Dec cultures (ID‐Dec: 475.1 ± 134.7 vs. Dec: 347.5 ± 98 pg/mL, p < 0.05). Conclusions: Although remaining in a tolerogenic profile compatible with DC‐10, DCs can differentially respond to decidual secreted factors based on embryo quality, changing their secretome. These results suggest that in the presence of arrested embryo, DCs could differentially shape the immunological microenvironment, contributing to arrested embryo clearance during the menstrual phase. [ABSTRACT FROM AUTHOR]

Published
2024
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9. miRNAs associated to endoplasmic reticulum stress and unfolded protein response during decidualization

Author

Soczewski, Elizabeth, primary, Murrieta-Coxca, José Martin, additional, Miranda, Lucas, additional, Fuentes-Zacarías, Paulina, additional, Gutiérrez-Samudio, Ruby, additional, Grasso, Esteban, additional, Marti, Marcelo, additional, Leirós, Claudia Pérez, additional, Morales-Prieto, Diana, additional, Markert, Udo R., additional, and Ramhorst, Rosanna, additional

Published
2023
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12. Extracellular vesicles of first trimester trophoblast cell line overexpressing VPAC2 induce anti-inflammatory signals in HB cell and maternal monocytes

Author

Paparini, Daniel E., primary, Grasso, Esteban N., additional, Vota, Daiana, additional, Hauk, Vanesa, additional, Merech, Fátima, additional, Lara, Brenda, additional, Izbizky, Gustavo, additional, Abasolo, Juan Ignacio, additional, Ramhorst, Rosanna, additional, and Leirós, Claudia Pérez, additional

Published
2022
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14. Endoplasmic reticulum stress induces an inflammatory response: Potential regulation by miRNAs

Author

Soczewski, Elizabeth, primary, Murrieta-Coxca, José Martin, additional, Zacarías-Fuentes, Paulina, additional, Gutiérrez-Samudio, Ruby, additional, Miranda, Lucas, additional, Grasso, Esteban, additional, Martí, Marcelo, additional, Morales-Prieto, Diana, additional, Leirós, Claudia Pérez, additional, Market, Udo, additional, and Ramhorst, Rosanna, additional

Published
2022
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15. Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period

Author

Fernández, Laura, primary, Grasso, Esteban, additional, Soczewski, Elizabeth, additional, Gori, Soledad, additional, Calo, Guillermina, additional, Hauk, Vanesa, additional, Sabbione, Florencia, additional, Gallino, Lucila, additional, Martínez, Gustavo, additional, Irigoyen, Marcela, additional, Bestach, Yesica, additional, Pérez Leirós, Claudia, additional, and Ramhorst, Rosanna, additional

Published
2021
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17. Placental extracellular vesicles: their potential as biomarkers of gestational complications

Author

Lara, Brenda Ayelen, Merech, Fátima Isabel, Vota, Daiana Marina, Calo, Guillermina, Soczewski, Elizabeth Victoria, Grasso, Esteban Nicolas, Perez Leiros, Claudia, and Hauk, Vanesa Cintia

Subjects
placenta, patologias gestacionales, purl.org/becyt/ford/3 [https], purl.org/becyt/ford/3.1 [https], vesiculas extracelulares
Abstract

Las vesículas extracelulares son importantes mediadores de la comunicación intercelular. Durante la gestación,diversos tipos celulares placentarios como no placentariossecretan vesículas extracelulares a la circulación. Se ha demostrado que las células trofoblásticas liberan permanentemente a la circulación materna vesículas extracelularescargadas con diversas moléculas que modulan la función delas células trofoblásticas, inmunes y vasculares, entre otras.Las complicaciones gestacionales que afectan la placentación, como la restricción del crecimiento intrauterino(RCIU) y la preeclampsia (PE), son un problema de saludpública mundial, ya que son condiciones que contribuyen,en alto grado, a la morbimortalidad materna y neonatal.Hasta ahora, no se dispone de pruebas clínicas quepermitan anticipar el diagnóstico y/o proveer indicadorespredictivos para identificar a las madres con mayor riesgode desarrollar estas complicaciones. En los últimos años,se ha demostrado el potencial de las vesículas extracelulares y su contenido como potenciales biomarcadoresde distintas patologías, por lo que su aplicación despiertaespecial interés en las complicaciones del embarazo. Extracellular vesicles are significant mediators of cellto-cell communication. During pregnancy, placental and non-placental cell types release extracellular vesicles into circulation. Is has been demonstrated that trophoblast cells are continuously releasing vesicles loaded with factors modulating trophoblast, immune and vascular functions. Gestational complications associated to impaired placentation, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), are a global public health problem since they are major contributors to maternal and neonatal morbidity and mortality. Currently, there are no clinical tests that allow early diagnosis and/or provide predictive markers to identify mothers at higher risk of developing these complications. The potential of extracellular vesicles and their content as biomarkers for different pathologies has been demonstrated. For this reason nowadays their application in gestational complications is of special interest. Fil: Lara, Brenda Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Soczewski, Elizabeth Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Published
2020

20. Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy

Author

Paparini, Daniel Esteban, primary, Grasso, Esteban, additional, Fernandez, Laura del Carmen, additional, Merech, Fátima, additional, Weingrill‐Barbano, Rodrigo, additional, Correa‐Silva, Simone, additional, Izbizky, Gustavo, additional, Abasolo, José Ignacio, additional, Hauk, Vanesa, additional, Ramhorst, Rosanna, additional, Bevilaqcua, Estela, additional, and Pérez Leirós, Claudia, additional

Published
2020
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23. Uso preferencial de plantas medicinales sobre medicamentos de venta libre en la comunidad de UNLaM

Author

Balducci D’Orta, María Laura, Calo, Guillermina, Coria Costenla, Vanesa, Dastugue, Milagros, Lang, Fabián, Grasso, Esteban, Paparini, Daniel, Savino, Antonio, Patrinos, Agustín, Pathauer, Florencia, Rodríguez, Saúl Marcelo, Del Pino, Verónica, Rodríguez, Saúl Marcelo, and Del Pino, Verónica

Subjects
MEDICINA ALTERNATIVA, 615.53, TERAPIAS COMPLEMENTARIAS, PLANTAS MEDICINALES, MATERIAL TERAPEUTICO, MEDICINA CON HIERBAS, PRODUCTOS FARMACEUTICOS
Abstract

Hace menos de un siglo que la población dispone de medicinas, vacunas y diferentes tratamientos avalados por la evidencia científica y utilizados por la medicina actual; estos avances han permitido aumentar considerablemente los años de esperanza de vida en general. La pregunta que surge es, ¿cómo se solucionaban o aliviaban las dolencias en épocas más remotas? Podemos pensar que utilizaban otros tipos de productos obtenidos de la naturaleza: plantas, hierbas, hongos, sustancias de origen animal, etc. Este sistema tradicional basado en la utilización de productos naturales no se perdió, sino que se sustenta en el saber popular e implica un conjunto de conocimientos, creencias, prácticas y recursos provenientes de este saber en un contexto sociocultural particular, y de los que hace uso la población de un colectivo para resolver de forma empírica algunos problemas de salud a pesar de la existencia y del alcance de la medicina científica (Menéndez, et al, 1994). El objetivo de la investigación es relevar las plantas que se utilizan como remedios naturales, para qué tipo de dolencias, y describir la población usuaria de esta opción en comparación con los que prefieren el uso de medicamentos farmacéuticos. Para la siguiente investigación se recolectaron datos mediante encuestas anónimas. Observamos cuales son los RN más utilizados y para qué tipo de dolencias son utilizados. Determinamos los motivos por los cuales se elige esta opción frente a medicamentos de farmacia; estudiamos los grupos en ambos casos sin encontrar diferencias significativas. La población con menos ingresos y que se atiende en hospitales públicos utiliza los RN de la misma forma que los de ingresos superiores con prepagas u obra social. El hábito de usar los RN tiene un componente que se transmite de generación en generación. Se observaron diferencias significativas, siendo mayor el uso de RN cuando sus padres también lo usaban. Nuestra hipótesis es que hay una tendencia a la medicalización; se exige una respuesta rápida y efectiva. Este comportamiento lleva a una pérdida del uso de RN y mengua su transmisión a las siguientes generaciones. Fil: Balducci D’Orta, María Laura. Universidad Nacional de La Matanza; Argentina Fil: Calo, Guillermina. Universidad Nacional de La Matanza; Argentina Fil: Coria Costenla, Vanesa. Universidad Nacional de La Matanza; Argentina Fil: Dastugue, Milagros. Universidad Nacional de La Matanza; Argentina Fil: Lang, Fabián. Universidad Nacional de La Matanza; Argentina Fil: Grasso, Esteban. Universidad Nacional de La Matanza; Argentina Fil: Paparini, Daniel. Universidad Nacional de La Matanza; Argentina Fil: Savino, Antonio. Universidad Nacional de La Matanza; Argentina Fil: Patrinos, Agustín. Universidad Nacional de La Matanza; Argentina Fil: Pathauer, Florencia. Universidad Nacional de La Matanza; Argentina Fil: Rodríguez, Saúl Marcelo. Universidad Nacional de La Matanza; Argentina Fil: Del Pino, Verónica. Universidad Nacional de La Matanza; Argentina

Published
2020

24. Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period.

Author

Fernández, Laura, Grasso, Esteban, Soczewski, Elizabeth, Gori, Soledad, Calo, Guillermina, Hauk, Vanesa, Sabbione, Florencia, Gallino, Lucila, Martínez, Gustavo, Irigoyen, Marcela, Bestach, Yesica, Pérez Leirós, Claudia, and Ramhorst, Rosanna

Subjects
*HUMAN embryos, *NATURAL selection, *REGULATORY T cells, *INFLAMMATION, *BLASTOCYST
Abstract

Problem: Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. Method of Study: We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl‐cAMP, then treated with human blastocysts‐conditioned media (BCM) classified according to their quality. Results: Decidualized cells treated with BCM from impaired developed blastocysts increased IL‐1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. Conclusion: Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo‐endometrial dialogue. [ABSTRACT FROM AUTHOR]

Published
2022
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25. Control of the inflammatory response during pregnancy: Potential role of VIP as a regulatory peptide

Author

Ramhorst, Rosanna Elizabeth, Calo, Guillermina, Paparini, Daniel Esteban, Vota, Daiana Marina, Hauk, Vanesa Cintia, Gallino, Lucila, Merech, Fátima Isabel, Grasso, Esteban Nicolas, and Perez Leiros, Claudia

Subjects
Medicina Básica, PREGNANCY, CIENCIAS MÉDICAS Y DE LA SALUD, VASOACTIVE INTESTINAL POLYPEPTIDE, TROPHOBLAST CELL LINES, IMMUNE HOMEOSTASIS, Inmunología
Abstract

A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti-inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. Fil: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gallino, Lucila. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fatima. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Published
2019
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26. VIP Promotes Recruitment of Tregs to the Uterine–Placental Interface During the Peri-Implantation Period to Sustain a Tolerogenic Microenvironment

Author

Gallino, Lucila, primary, Hauk, Vanesa, additional, Fernández, Laura, additional, Soczewski, Elizabeth, additional, Gori, Soledad, additional, Grasso, Esteban, additional, Calo, Guillermina, additional, Saraco, Nora, additional, Berensztein, Esperanza, additional, Waschek, James A., additional, Pérez Leirós, Claudia, additional, and Ramhorst, Rosanna, additional

Published
2020
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29. The decidualization by VIP conditions endometrial receptivity and immune microenvironment through Reticular Stress and Unfolded Protein Response

Author

Gori, Soledad, primary, Soczewski, Elizabeth, additional, Grasso, Esteban, additional, Fernandez, Laura, additional, Gallino, Lucila, additional, Irigoyen, Marcela, additional, Lobo, Thalita F., additional, Salamone, Gabriela, additional, Mattar, Rosiane, additional, Daher, Silvia, additional, Leiros, Claudia Perez, additional, and Ramhorst, Rosanna, additional

Published
2019
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32. Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy.

Author

Paparini, Daniel Esteban, Grasso, Esteban, Fernandez, Laura del Carmen, Merech, Fátima, Weingrill‐Barbano, Rodrigo, Correa‐Silva, Simone, Izbizky, Gustavo, Abasolo, José Ignacio, Hauk, Vanesa, Ramhorst, Rosanna, Bevilaqcua, Estela, and Pérez Leirós, Claudia

Subjects
*VASOACTIVE intestinal peptide, *MONOCYTES, *HEALING, *HOMEOSTASIS, *WOUND healing
Abstract

Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP). Methods: Peripheral blood monocytes were isolated from pregnant and non‐pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT‐qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE‐labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas. Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP‐conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP‐induced decidual factors. Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Control of the inflammatory response during pregnancy: potential role of VIP as a regulatory peptide.

Author

Ramhorst, Rosanna, Calo, Guillermina, Paparini, Daniel, Vota, Daiana, Hauk, Vanesa, Gallino, Lucila, Merech, Fatima, Grasso, Esteban, and Leirós, Claudia Pérez

Subjects
INFLAMMATION, PREGNANCY, VASOACTIVE intestinal peptide, CELL communication, MACROPHAGES
Abstract

A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti‐inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Neuroimmune aspects of Sjogren's syndrome: role of VIP/VPAC system in immune and salivary gland epithelial cell function

Author

Fraccaroli Laura, Paparini Daniel, Grasso Esteban, Calafat Mario, Ramhorst Rosanna, Hauk Vanesa, and Perez Leiros Claudia

Subjects
Pharmacology, Autoimmune disease, Salivary gland, Vasoactive intestinal peptide, Epithelial Cells, Lacrimal gland, Nod, Disease, Biology, medicine.disease, Salivary Glands, Disease Models, Animal, Mice, medicine.anatomical_structure, Immune system, Sjogren's Syndrome, Immune System, Drug Discovery, Immunology, medicine, Animals, Humans, Homeostasis, Vasoactive Intestinal Peptide
Abstract

Sjogren's syndrome (SS) is a chronic inflammatory disease characterized by salivary and lacrimal gland dysfunction although extraglandular manifestations are also found. Suitable study models and in vitro cell culture designs are used to approach SS pathogenic mechanisms. Cellular and molecular pathways involved in gland homeostasis loss and the autoimmune response are focused in the search of novel drug targets and biomarkers. Vasoactive intestinal peptide (VIP) has trophic, pro-secretory and immunomodulatory effects in several chronic and autoimmune disease models. Here we review evidence pointing to its role as an endogenous modulator of gland homeostasis at early stages of the disease. Particularly, mechanisms involving VIP/VPAC system in the course of salivary function impairment in the non obese diabetic (NOD) mouse model of Sjogren's syndrome are described.

Published
2013

45. Human trophoblast cell migration and invasion are induced by endogenous vasoactive intestinal peptide (VIP) through autocrine circuits and VPAC2 overexpression

Author

Grasso Esteban, Hauk Vanesa, Perez Leiros Claudia, Vota Daiana, Paparini Daniel, Ramhorst Rosanna, Varone Cecilia, and Toro Ayelen

Subjects
medicine.medical_specialty, Endocrinology, Reproductive Medicine, Internal medicine, Vasoactive intestinal peptide, medicine, Trophoblast cell migration, Obstetrics and Gynecology, Endogeny, Biology, Autocrine signalling, Developmental Biology, Cell biology
Published
2015
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49. VIP contribution to the decidualization program: regulatory T cell recruitment.

Author

Grasso, Esteban Esteban, Paparini, Daniel, Agüero, Mariana, Mor, Gil, Leirós, Claudia Pérez, and Ramhorst, Rosanna

Subjects
PREGNANCY, UTERUS, LEUCOCYTES, CYTOKINES, TROPHOBLAST, IMMUNE response
Abstract

During early pregnancy, the human uterus undergoes profound tissue remodeling characterized by leukocyte invasion and production of proinflammatory cytokines, followed by tissue repair and tolerance maintenance induction. Vasoactive intestinal peptide (VIP) is produced by trophoblast cells and modulates the maternal immune response toward a tolerogenic profile. Here, we evaluated the contribution of the VIP/VPAC to endometrial renewal, inducing decidualization and the recruitment of induced regulatory T cells (iTregs) that accompany the implantation period. For that purpose, we used an in vitro model of decidualization with a human endometrial stromal cell line (HESC) stimulated with progesterone (P4) and lipopolysaccharide (LPS) simulating the inflammatory response during implantation and human iTregs (CD4+CD25+FOXP3+) differentiated from naïve T cells obtained from peripheral blood mononuclear cells of fertile women. We observed that VIP and its receptor VPAC1 are constitutively expressed in HESCs and that P4 increased VIP expression. Moreover, in HESC VIP induced expression of RANTES (CCL5), one of the main chemokines involved in T cell recruitment, and this effect is enhanced by the presence of P4 and LPS. Finally, assays of the migration of iTregs toward conditioned media from HESCs revealed that endogenous VIP production induced by P4 and LPS and RANTES production were involved, as anti-RANTES neutralizing Ab or VIP antagonist prevented their migration. We conclude that VIPmay have an active role in the decidualization process, thus contributing to recruitment of iTregs toward endometrial stromal cells by increasing RANTES expression in a P4-dependent manner. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Ovarian premature aging: VIP as key regulator of fibro-inflammation and foamy macrophages generation.

Author

Castagnola L, Gallino L, Schafir A, Vota D, Grasso E, Gori S, Waschek J, Parborell F, Leirós CP, Hauk V, and Ramhorst R

Abstract

Ovarian aging is associated with fibro-inflammation, contributing to the decline in oocyte count and quality. Given the immunomodulatory properties of the vasoactive intestinal peptide (VIP) in the reproductive tract, we investigated its role in maintaining ovarian immune homeostasis and preventing premature aging. We evaluated young VIP knockout (KO) mice, comparing them to young wild type (WT) females, for signs of premature aging. Histological staining revealed aberrant ovarian morphology in VIP KO mice, characterized by increased atretic follicles and decreased ovarian reserve compared to WT controls. Moreover, VIP KO ovaries showed reduced vascularization, increased collagen deposition and elevated ROS and IL-1β levels. Foamy macrophages were significantly predominant, indicating premature aging in young VIP KO ovaries. To determine potential mechanisms behind these pathogenic changes, we conditioned peritoneal macrophages from young WT or VIP KO mice in vitro with ovarian-conditioned media from young WT or VIP KO mice to mimic the respective ovarian microenvironment. When WT or VIP KO peritoneal macrophages were conditioned with ovarian media from their respective genotypes, lipid droplet accumulation increased compared to control medium. In cross-genotype experiments, WT macrophages conditioned with media from VIP KO ovaries selectively accumulated higher levels of lipid droplets, whereas no differences were observed in VIP KO macrophages conditioned with WT ovarian media. This suggests that VIP KO macrophages are uniquely sensitized to the inflammatory environment of VIP KO ovaries, implicating both ovarian factors and macrophage status. These findings highlight the role of VIP in preventing fibro-inflammation, thereby preserving ovarian health and preventing premature aging., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Published
2025
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