Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice

Abstract With emerging evidence connecting cholesterol dysregulation with disturbed pulmonary homeostasis, we are wondering if diet induced hypercholesterolemia would influence the susceptibility to chemical induced lung tumorigenesis in mice. Six to eight week-old male C57BL/6J mice were fed with e...

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Autores principales:	Ting Chen, Lei Lu, Cai Xu, Xiaojing Lin, Yuet-kin Leung, Shuk-Mei Ho, Xiong Z. Ruan, Xuemei Lian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9102da6f593f446689d11654f7e7b9a0
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spelling	oai:doaj.org-article:9102da6f593f446689d11654f7e7b9a02021-12-02T15:05:31ZInhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice10.1038/s41598-017-05053-12045-2322https://doaj.org/article/9102da6f593f446689d11654f7e7b9a02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05053-1https://doaj.org/toc/2045-2322Abstract With emerging evidence connecting cholesterol dysregulation with disturbed pulmonary homeostasis, we are wondering if diet induced hypercholesterolemia would influence the susceptibility to chemical induced lung tumorigenesis in mice. Six to eight week-old male C57BL/6J mice were fed with either a high-cholesterol atherogenic diet (HCD) or matching normal diet (ND), respectively. Following 3 weeks diet adapting, a multi-dose intraperitoneal injections of ethyl carbamate (urethane, 1 g/kg body weight) were established and lung tumorigenesis assessments were taken after 15 weeks latency period. Compared to the urethane treated ND-fed mice, the HCD-fed mice exhibited significantly decreased lung tumor multiplicity and attenuated pulmonary inflammation, which including reduced influx of leukocytes and down regulated tumor-promoting cyto-/chemokine profile in bronchoalveolar lavage fluid, decreased TLR2/4 expression and NF-κB activation in the lung. As a sensor regulating intracellular cholesterol homeostasis, nuclear receptor LXR-α was up-regulated significantly in the urethane treated HCD-fed mice lungs compared to the ND-fed mice lungs, accompanied with decreased pulmonary free cholesterol content and suppressed tumor cell proliferation. These results suggested that intrapulmonary cholesterol homeostasis, other than systematic cholesterol level, is important in lung tumorigenesis, and LXR activation might partly contribute to the inhibitory role of atherogenic diet on lung tumorigenesis.Ting ChenLei LuCai XuXiaojing LinYuet-kin LeungShuk-Mei HoXiong Z. RuanXuemei LianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ting Chen Lei Lu Cai Xu Xiaojing Lin Yuet-kin Leung Shuk-Mei Ho Xiong Z. Ruan Xuemei Lian Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
description	Abstract With emerging evidence connecting cholesterol dysregulation with disturbed pulmonary homeostasis, we are wondering if diet induced hypercholesterolemia would influence the susceptibility to chemical induced lung tumorigenesis in mice. Six to eight week-old male C57BL/6J mice were fed with either a high-cholesterol atherogenic diet (HCD) or matching normal diet (ND), respectively. Following 3 weeks diet adapting, a multi-dose intraperitoneal injections of ethyl carbamate (urethane, 1 g/kg body weight) were established and lung tumorigenesis assessments were taken after 15 weeks latency period. Compared to the urethane treated ND-fed mice, the HCD-fed mice exhibited significantly decreased lung tumor multiplicity and attenuated pulmonary inflammation, which including reduced influx of leukocytes and down regulated tumor-promoting cyto-/chemokine profile in bronchoalveolar lavage fluid, decreased TLR2/4 expression and NF-κB activation in the lung. As a sensor regulating intracellular cholesterol homeostasis, nuclear receptor LXR-α was up-regulated significantly in the urethane treated HCD-fed mice lungs compared to the ND-fed mice lungs, accompanied with decreased pulmonary free cholesterol content and suppressed tumor cell proliferation. These results suggested that intrapulmonary cholesterol homeostasis, other than systematic cholesterol level, is important in lung tumorigenesis, and LXR activation might partly contribute to the inhibitory role of atherogenic diet on lung tumorigenesis.
format	article
author	Ting Chen Lei Lu Cai Xu Xiaojing Lin Yuet-kin Leung Shuk-Mei Ho Xiong Z. Ruan Xuemei Lian
author_facet	Ting Chen Lei Lu Cai Xu Xiaojing Lin Yuet-kin Leung Shuk-Mei Ho Xiong Z. Ruan Xuemei Lian
author_sort	Ting Chen
title	Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
title_short	Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
title_full	Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
title_fullStr	Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
title_full_unstemmed	Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice
title_sort	inhibition role of atherogenic diet on ethyl carbamate induced lung tumorigenesis in c57bl/6j mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9102da6f593f446689d11654f7e7b9a0
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_version_	1718388780922044416

Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice

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