Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard

Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines,...

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Main Authors:	Badr, Mostafa Z., Shnyra, Alexander, Zoubine, Mikhail, Norkin, Maxim, Herndon, Betty, Quinn, Tim, Miranda, Roberto N., Cunningham, Michael L., Molteni, Agostino
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246061/

id	pubmed-2246061
recordtype	oai_dc
spelling	pubmed-22460612008-03-04 Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard Badr, Mostafa Z. Shnyra, Alexander Zoubine, Mikhail Norkin, Maxim Herndon, Betty Quinn, Tim Miranda, Roberto N. Cunningham, Michael L. Molteni, Agostino Research Article Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFNγ+ Th1 and IL-4+ Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPARα-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated. Hindawi Publishing Corporation 2007 2008-01-01 /pmc/articles/PMC2246061/ /pubmed/18566640 http://dx.doi.org/10.1155/2007/49671 Text en Copyright © 2007 Mostafa Z. Badr et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Badr, Mostafa Z. Shnyra, Alexander Zoubine, Mikhail Norkin, Maxim Herndon, Betty Quinn, Tim Miranda, Roberto N. Cunningham, Michael L. Molteni, Agostino
spellingShingle	Badr, Mostafa Z. Shnyra, Alexander Zoubine, Mikhail Norkin, Maxim Herndon, Betty Quinn, Tim Miranda, Roberto N. Cunningham, Michael L. Molteni, Agostino Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
author_facet	Badr, Mostafa Z. Shnyra, Alexander Zoubine, Mikhail Norkin, Maxim Herndon, Betty Quinn, Tim Miranda, Roberto N. Cunningham, Michael L. Molteni, Agostino
author_sort	Badr, Mostafa Z.
title	Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
title_short	Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
title_full	Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
title_fullStr	Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
title_full_unstemmed	Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard
title_sort	phthalate-induced liver protection against deleterious effects of the th1 response: a potentially serious health hazard
description	Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFNγ+ Th1 and IL-4+ Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPARα-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated.
publisher	Hindawi Publishing Corporation
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246061/
_version_	1611439361059979264

Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard

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