The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Immunotoxicity of Perfluorooctanoic Acid and Perfluorooctane Sulfonate and the Role of Peroxisome Proliferator-Activated Receptor Alpha
Abstract
Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmentally widespread and persistent chemicals with multiple toxicities reported in experimental animals and humans. These compounds can trigger biological activity by activating the alpha isotype of peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors that regulate gene expression; however, some biological effects may occur independently of the receptor. Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) modulates lipid and glucose homeostasis, cell proliferation and differentiation, and inflammation. Reported immunomodulation in experimental animals exposed to PFOA and PFOS has included altered inflammatory responses, production of cytokines and other proteins, reduced lymphoid organ weights, and altered antibody synthesis. Mounting experimental animal evidence suggests PPARalpha independence of some immune effects. This evidence originates primarily from studies with PPARalpha knockout models exposed to PFOA that demonstrate hepatic peroxisome proliferation, reduced lymphoid organ weights, and altered antibody synthesis. As human PPARalpha expression is significantly less than that of rodents, potential PPARalpha independence indicates that future research must explore mechanisms of action of these compounds, including PPARalpha-dependent and -independent pathways. This multiauthored review contains brief descriptions of current and recently published work exploring immunomodulation by PFOA and PFOS, as well as a short overview of other PPARalpha ligands of therapeutic and environmental interest.
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“Other studies have suggested that alterations in IgG secretion in mice exposed to PFOA may occur independently of systemic toxicity and stress-related corticosterone increases (DeWitt et al., 2009a), noting that IgG secretion in the BT system in BioMAP was unaffected by PFOA.”
Influential
Metadata
- Authors
- DeWitt, J. C., Shnyra, A., Badr, M. Z., Loveless, S. E., Hoban, D., Frame, S. R., Cunard, R., Anderson, S. E., Meade, B. J., Peden-Adams, M. M., Luebke, R. W., & Luster, M. I.
- Venue
- Critical Reviews in Toxicology
- Publisher
- Informa UK Limited
- Published
- 2009-01
- Volume
- 39
- Issue
- 1
- Pages
- 76-94
- ISSN
- 0045-6446 (ISSN-L)
- 1040-8444
- 1547-6898
- OpenAlex
- W2099251250
- Cited by
- 266
- References
- 11
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- closed
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