Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice

Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) usin...

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Autores principales:	Annegret Glasow, Ina Patties, Nicholas D. Priest, Ronald E. J. Mitchel, Guido Hildebrandt, Katrin Manda
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	low dose irradiation ApoE inflammation endothelial cytokine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1da165c7c1974c26970ed2de992897c2
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spelling	oai:doaj.org-article:1da165c7c1974c26970ed2de992897c22021-11-25T17:13:18ZDose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice10.3390/cells101132512073-4409https://doaj.org/article/1da165c7c1974c26970ed2de992897c22021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3251https://doaj.org/toc/2073-4409Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE−/−) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFβ, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFβ) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE−/− mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFβ at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE−/− mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFβ increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.Annegret GlasowIna PattiesNicholas D. PriestRonald E. J. MitchelGuido HildebrandtKatrin MandaMDPI AGarticlelow doseirradiationApoEinflammationendothelialcytokineBiology (General)QH301-705.5ENCells, Vol 10, Iss 3251, p 3251 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	low dose irradiation ApoE inflammation endothelial cytokine Biology (General) QH301-705.5
spellingShingle	low dose irradiation ApoE inflammation endothelial cytokine Biology (General) QH301-705.5 Annegret Glasow Ina Patties Nicholas D. Priest Ronald E. J. Mitchel Guido Hildebrandt Katrin Manda Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
description	Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE−/−) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFβ, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFβ) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE−/− mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFβ at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE−/− mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFβ increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.
format	article
author	Annegret Glasow Ina Patties Nicholas D. Priest Ronald E. J. Mitchel Guido Hildebrandt Katrin Manda
author_facet	Annegret Glasow Ina Patties Nicholas D. Priest Ronald E. J. Mitchel Guido Hildebrandt Katrin Manda
author_sort	Annegret Glasow
title	Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
title_short	Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
title_full	Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
title_fullStr	Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
title_full_unstemmed	Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice
title_sort	dose and dose rate-dependent effects of low-dose irradiation on inflammatory parameters in apoe-deficient and wild type mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1da165c7c1974c26970ed2de992897c2
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Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice

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