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: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2007-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2007/49671 |
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| author | Mostafa Z. Badr Alexander Shnyra Mikhail Zoubine Maxim Norkin Betty Herndon Tim Quinn Roberto N. Miranda Michael L. Cunningham Agostino Molteni |
| author_facet | Mostafa Z. Badr Alexander Shnyra Mikhail Zoubine Maxim Norkin Betty Herndon Tim Quinn Roberto N. Miranda Michael L. Cunningham Agostino Molteni |
| author_sort | Mostafa Z. Badr |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-3328e255bd34497b80782c0ea16ec52e |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2007-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-3328e255bd34497b80782c0ea16ec52e2025-08-20T03:55:22ZengWileyPPAR Research1687-47571687-47652007-01-01200710.1155/2007/4967149671Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health HazardMostafa Z. Badr0Alexander Shnyra1Mikhail Zoubine2Maxim Norkin3Betty Herndon4Tim Quinn5Roberto N. Miranda6Michael L. Cunningham7Agostino Molteni8Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City 64108, MO, USADepartment of Pharmacology and Microbiology, Kansas City University of Medicine and Biosciences, Kansas City 64106, MO, USADepartment of Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USADepartment of Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USADepartment of Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USADepartment of Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USADepartment of Pathology, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USALaboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, 27709, NC, USADepartment of Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City 64108, MO, USAInfection 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.http://dx.doi.org/10.1155/2007/49671 |
| spellingShingle | Mostafa Z. Badr Alexander Shnyra Mikhail Zoubine Maxim Norkin Betty Herndon Tim Quinn Roberto N. Miranda Michael L. Cunningham Agostino Molteni Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard PPAR Research |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2007/49671 |
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