2015
DOI: 10.3109/1547691x.2014.996682
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Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARαand T- and B-cell targeting

Abstract: T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to !3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPAR)-dependent and if suppression is associated with specific targeting of T-or B-cells, three separate experiments were conducted: (1) female PPAR constitutive knockout (PPAR KO; B6.129S4-Ppar tm1Gonz N12) and wild-type controls (WT; C57BL/6-Tac) expose… Show more

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Cited by 68 publications
(74 citation statements)
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“…Rather compelling evidence from animal studies linked PFASs to suppression of the primary antibody response, i.e. the antigen-specific IgM antibody production to T-cell-specific antigens in mice [9396]. Regarding metabolic effects, strong inverse associations between maternal PFOS with triglycerides, essential fatty acids and omega 3 and 6 fatty acids during pregnancy have been described [33].…”
Section: Discussionmentioning
confidence: 99%
“…Rather compelling evidence from animal studies linked PFASs to suppression of the primary antibody response, i.e. the antigen-specific IgM antibody production to T-cell-specific antigens in mice [9396]. Regarding metabolic effects, strong inverse associations between maternal PFOS with triglycerides, essential fatty acids and omega 3 and 6 fatty acids during pregnancy have been described [33].…”
Section: Discussionmentioning
confidence: 99%
“…However, PFOA and PFOS also induced gene expression changes that were independent of PPARa for xenobiotic and fatty acid metabolism, inflammation, and cell cycle regulation in PPARa null mice (Rosen et al , 2010. Exposure to PFOA suppressed the T-cell dependent antigen response to SRBC in both PPARa knockout and wild-type C57BL/6 mice (DeWitt et al 2016), while PFOS inhibited IL-2 production in stimulated human Jurkat T-cells in the presence and absence of the PPARa-antagonist GW6471 (Midgett et al 2015), and inhibited TNFa and IL-8 secretion in stimulated THP-1 cells (pro-myelocytic cell line) in the presence and absence of PPARa siRNA (Corsini et al 2011). In vitro, PFDA exposure decreased secretion of TNFa and IL-6 in stimulated human peripheral blood leukocytes (hPBL) and in THP-1 cells, decreased secretion of interferon (IFN)-c by stimulated hPBL, and inhibited NF-jB activation in stimulated THP-1 cells.…”
Section: Treatmentmentioning
confidence: 96%
“…has been confirmed to be a prominent (but not only) mechanism of action for many of the prevalent toxicities observed in rodents with PFOS and PFOA [218][219][220]235, 262-268], including hepatomegaly and peroxisome proliferation; developmental toxicity [229,239] immunotoxicity [225]; endocrine disruption [227]; tumorigenicity [269]. The binding sites of PFOA, PFOS and PFHxS in the PPAR and other nuclear receptor proteins have been modeled [270].…”
Section: Animals Experience a Range Of Adverse Effects Usually At Himentioning
confidence: 97%
“…Effects on the immune system include reduced lymphoid organ (thymus and spleen) weights and lymphoid cell numbers, altered T-cell populations, reduced specific antibody production, altered inflammatory responses and production of cytokines and other proteins [217, 224,225].…”
Section: Animals Experience a Range Of Adverse Effects Usually At Himentioning
confidence: 99%