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Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury

Recently, we discovered that the cytokine interleukin-6 (IL-6) acts as a pituitary stem cell-activating factor, both when administered in vivo and when added to stem cell organoid cultures in vitro. Moreover, its expression, predominantly localized in the gland’s stem and mesenchymal cells, promptly...

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Autores principales: Laporte, Emma, De Vriendt, Silke, Hoekx, Julie, Vankelecom, Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815540/
https://www.ncbi.nlm.nih.gov/pubmed/36619565
http://dx.doi.org/10.3389/fendo.2022.1092063
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author Laporte, Emma
De Vriendt, Silke
Hoekx, Julie
Vankelecom, Hugo
author_facet Laporte, Emma
De Vriendt, Silke
Hoekx, Julie
Vankelecom, Hugo
author_sort Laporte, Emma
collection PubMed
description Recently, we discovered that the cytokine interleukin-6 (IL-6) acts as a pituitary stem cell-activating factor, both when administered in vivo and when added to stem cell organoid cultures in vitro. Moreover, its expression, predominantly localized in the gland’s stem and mesenchymal cells, promptly increases following damage in the adult pituitary, leading to stem-cell proliferative activation. Given these findings that IL-6 is involved in pituitary stem cell regulation, we addressed the question whether the cytokine has an impact on the pituitary phenotype during active phases of the gland’s remodeling, in particular embryonic development and neonatal maturation, as well as during homeostasis at adulthood and aging, all unknown today. Using the IL-6 knock-out (KO) mouse model, we show that IL-6 is dispensable for pituitary embryonic and neonatal endocrine cell development, as well as for hormonal cell homeostasis in adult and aging glands. The findings match the absence of effects on the stem cell compartment at these stages. However, using this IL-6 KO model, we found that IL-6 is needed for the acute stem-cell proliferative activation reaction upon pituitary injury. Intriguingly, regeneration still occurs which may be due to compensatory behavior by other cytokines which are upregulated in the damaged IL-6 KO pituitary, although at lower but prolonged levels, which might lead to a delayed (and less forceful) stem cell response. Taken together, our study revealed that IL-6 is dispensable for normal pituitary development and homeostasis but plays a key role in the prompt stem cell activation upon local damage, although its presence is not essentially needed for the final regenerative realization.
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spelling pubmed-98155402023-01-06 Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury Laporte, Emma De Vriendt, Silke Hoekx, Julie Vankelecom, Hugo Front Endocrinol (Lausanne) Endocrinology Recently, we discovered that the cytokine interleukin-6 (IL-6) acts as a pituitary stem cell-activating factor, both when administered in vivo and when added to stem cell organoid cultures in vitro. Moreover, its expression, predominantly localized in the gland’s stem and mesenchymal cells, promptly increases following damage in the adult pituitary, leading to stem-cell proliferative activation. Given these findings that IL-6 is involved in pituitary stem cell regulation, we addressed the question whether the cytokine has an impact on the pituitary phenotype during active phases of the gland’s remodeling, in particular embryonic development and neonatal maturation, as well as during homeostasis at adulthood and aging, all unknown today. Using the IL-6 knock-out (KO) mouse model, we show that IL-6 is dispensable for pituitary embryonic and neonatal endocrine cell development, as well as for hormonal cell homeostasis in adult and aging glands. The findings match the absence of effects on the stem cell compartment at these stages. However, using this IL-6 KO model, we found that IL-6 is needed for the acute stem-cell proliferative activation reaction upon pituitary injury. Intriguingly, regeneration still occurs which may be due to compensatory behavior by other cytokines which are upregulated in the damaged IL-6 KO pituitary, although at lower but prolonged levels, which might lead to a delayed (and less forceful) stem cell response. Taken together, our study revealed that IL-6 is dispensable for normal pituitary development and homeostasis but plays a key role in the prompt stem cell activation upon local damage, although its presence is not essentially needed for the final regenerative realization. Frontiers Media S.A. 2022-12-22 /pmc/articles/PMC9815540/ /pubmed/36619565 http://dx.doi.org/10.3389/fendo.2022.1092063 Text en Copyright © 2022 Laporte, De Vriendt, Hoekx and Vankelecom https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Laporte, Emma
De Vriendt, Silke
Hoekx, Julie
Vankelecom, Hugo
Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title_full Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title_fullStr Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title_full_unstemmed Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title_short Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
title_sort interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815540/
https://www.ncbi.nlm.nih.gov/pubmed/36619565
http://dx.doi.org/10.3389/fendo.2022.1092063
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