TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
<h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implant...
Guardado en:
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2011
|
Materias: | |
Acceso en línea: | https://doaj.org/article/5705640e236f4589842bfc1a521a9b7d |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:5705640e236f4589842bfc1a521a9b7d |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:5705640e236f4589842bfc1a521a9b7d2021-11-18T07:00:40ZTWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.1932-620310.1371/journal.pone.0014497https://doaj.org/article/5705640e236f4589842bfc1a521a9b7d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21249128/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity.<h4>Methodology/principal findings</h4>Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions.<h4>Conclusions/significance</h4>TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human.Marie PetitbaratMona RahmatiValérie SérazinSylvie DubanchetCorinne MorvanRobert WainerPhilippe de MazancourtGérard ChaouatJean-Michel FoidartCarine MunautNathalie LédéePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14497 (2011) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Marie Petitbarat Mona Rahmati Valérie Sérazin Sylvie Dubanchet Corinne Morvan Robert Wainer Philippe de Mazancourt Gérard Chaouat Jean-Michel Foidart Carine Munaut Nathalie Lédée TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
description |
<h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity.<h4>Methodology/principal findings</h4>Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions.<h4>Conclusions/significance</h4>TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human. |
format |
article |
author |
Marie Petitbarat Mona Rahmati Valérie Sérazin Sylvie Dubanchet Corinne Morvan Robert Wainer Philippe de Mazancourt Gérard Chaouat Jean-Michel Foidart Carine Munaut Nathalie Lédée |
author_facet |
Marie Petitbarat Mona Rahmati Valérie Sérazin Sylvie Dubanchet Corinne Morvan Robert Wainer Philippe de Mazancourt Gérard Chaouat Jean-Michel Foidart Carine Munaut Nathalie Lédée |
author_sort |
Marie Petitbarat |
title |
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
title_short |
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
title_full |
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
title_fullStr |
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
title_full_unstemmed |
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. |
title_sort |
tweak appears as a modulator of endometrial il-18 related cytotoxic activity of uterine natural killers. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/5705640e236f4589842bfc1a521a9b7d |
work_keys_str_mv |
AT mariepetitbarat tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT monarahmati tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT valerieserazin tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT sylviedubanchet tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT corinnemorvan tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT robertwainer tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT philippedemazancourt tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT gerardchaouat tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT jeanmichelfoidart tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT carinemunaut tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers AT nathalieledee tweakappearsasamodulatorofendometrialil18relatedcytotoxicactivityofuterinenaturalkillers |
_version_ |
1718424040106885120 |