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Cited by 131Peroxisome Proliferator-Activated ReceptorsImmunotoxicology and immune responsesPer- and polyfluoroalkyl substances research

Involvement of the Peroxisome Proliferator-Activated Receptor Alpha in the Immunomodulation Caused by Peroxisome Proliferators in Mice

Yang, Qian, Xie, Yi, Alexson, Stefan E.H., Dean Nelson, B., DePierre, Joseph W.·2002·Biochemical Pharmacology
DOI 10.1016/s0006-2952(02)00923-1
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Abstract

Peroxisome proliferators (PPs) are a large class of structurally diverse chemicals, which includes drugs designed to improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin-resistance and atherosclerosis. We have recently demonstrated that exposure of rodents to potent PPs indirectly causes a number of immunomodulating effects, resulting in severe adaptive immunosuppression. Since the peroxisome proliferator-activated receptor alpha (PPARalpha) plays a central role in mediating the pleiotropic responses exerted by PPs, we have compared here the immunomodulating effects of the PPs perfluorooctanoic acid (PFOA) and Wy-14,643 in wild-type and PPARalpha-null mice. The reductions in spleen weight and in the number of splenocytes caused by PP treatment in wild-type mice was not observed in PPARalpha-null mice. Furthermore, the reductions in thymus weight and in the number of thymocytes were potently attenuated in the latter animals. Similarly, the dramatic decreases in the size of the CD4(+)CD8(+) population of cells in the thymus and in the number of thymocytes in the S and G2/M phases of the cell cycle observed in wild-type mice administered PPs were much less extensive in PPARalpha-null mice. Finally, in contrast to the case of wild-type animals, the response of splenocytes isolated from the spleen of PP-treated PPARalpha-null mice to appropriate T- or B-cell activators in vitro was not reduced. Altogether, these data indicate that PPARalpha plays a major role in the immunomodulation caused by PPs. The possible relevance of these changes to the alterations in plasma lipids also caused by PPs is discussed.

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Authors
Yang, Q., Xie, Y., Alexson, S. E. H., Dean Nelson, B., & DePierre, J. W.
Affiliations
  • Stockholm University (SE)
  • Karolinska Institutet (SE)
Corresponding author
Yang, Qian
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2002-05
Volume
63
Issue
10
Pages
1893-1900
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/s0006-2952(02)00923-1
OpenAlex
W2034901755
Cited by
131
References
41
Citations by year
2026: 1 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 11 · 2013: 5 · 2012: 6
FWCI
1.62
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Knut och Alice Wallenbergs Stiftelse
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Keywords
peroxisome proliferators, PPARα, immunomodulation, immunosuppression, perfluorooctanoic acid, Wy-14,643, PPARalpha-null mice, thymus, spleen, CD4+CD8+ thymocytes, T cell response, B cell response, plasma lipids, hypertriglyceridemia
MeSH terms
Adjuvants, Immunologic, Animals, Caprylates, Cell Cycle, Cell Division, Cells, Cultured, Fluorocarbons, Liver, Male, Mice, Inbred BALB C, Organ Size, Pyrimidines, Spleen, Thymus Gland, Transcription Factors, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Peroxisome Proliferators, Peroxisomes, Models, Animal, Mice

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