Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring

Yo Shimizu,1 Tsuyoshi Tsukada,2 Hiromi Sakata-Haga,2 Daisuke Sakai,3 Hiroki Shoji,3 Yutaka Saikawa,1 Toshihisa Hatta2 1Department of Pediatrics, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 2Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 3Department of Biol...

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Autores principales:	Shimizu Y, Tsukada T, Sakata-Haga H, Sakai D, Shoji H, Saikawa Y, Hatta T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	maternal immune activation liver necrosis immune overreaction unfolded protein response defects Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8a08ca48d8b84b49b1e84447ff1d4143
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spelling	oai:doaj.org-article:8a08ca48d8b84b49b1e84447ff1d41432021-12-02T12:14:54ZExposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring1178-7031https://doaj.org/article/8a08ca48d8b84b49b1e84447ff1d41432021-02-01T00:00:00Zhttps://www.dovepress.com/exposure-to-maternal-immune-activation-causes-congenital-unfolded-prot-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Yo Shimizu,1 Tsuyoshi Tsukada,2 Hiromi Sakata-Haga,2 Daisuke Sakai,3 Hiroki Shoji,3 Yutaka Saikawa,1 Toshihisa Hatta2 1Department of Pediatrics, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 2Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 3Department of Biology, Kanazawa Medical University, Uchinada, Ishikawa, JapanCorrespondence: Toshihisa HattaDepartment of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, JapanTel +81-76-281-8113Fax +81-76-218-8189Email thatta@kanazawa-med.ac.jpBackground: A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model.Materials and Methods: Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3– 4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined.Results: The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group.Conclusion: Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.Keywords: maternal immune activation, liver necrosis, immune overreaction, unfolded protein response defectsShimizu YTsukada TSakata-Haga HSakai DShoji HSaikawa YHatta TDove Medical Pressarticlematernal immune activationliver necrosisimmune overreactionunfolded protein response defectsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 355-365 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	maternal immune activation liver necrosis immune overreaction unfolded protein response defects Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	maternal immune activation liver necrosis immune overreaction unfolded protein response defects Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Shimizu Y Tsukada T Sakata-Haga H Sakai D Shoji H Saikawa Y Hatta T Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
description	Yo Shimizu,1 Tsuyoshi Tsukada,2 Hiromi Sakata-Haga,2 Daisuke Sakai,3 Hiroki Shoji,3 Yutaka Saikawa,1 Toshihisa Hatta2 1Department of Pediatrics, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 2Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 3Department of Biology, Kanazawa Medical University, Uchinada, Ishikawa, JapanCorrespondence: Toshihisa HattaDepartment of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, JapanTel +81-76-281-8113Fax +81-76-218-8189Email thatta@kanazawa-med.ac.jpBackground: A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model.Materials and Methods: Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3– 4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined.Results: The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group.Conclusion: Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.Keywords: maternal immune activation, liver necrosis, immune overreaction, unfolded protein response defects
format	article
author	Shimizu Y Tsukada T Sakata-Haga H Sakai D Shoji H Saikawa Y Hatta T
author_facet	Shimizu Y Tsukada T Sakata-Haga H Sakai D Shoji H Saikawa Y Hatta T
author_sort	Shimizu Y
title	Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
title_short	Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
title_full	Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
title_fullStr	Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
title_full_unstemmed	Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring
title_sort	exposure to maternal immune activation causes congenital unfolded protein response defects and increases the susceptibility to postnatal inflammatory stimulation in offspring
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8a08ca48d8b84b49b1e84447ff1d4143
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Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring

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