ToxSci Advance Access originally published online on June 26, 2008
Toxicological Sciences 2008 105(2):312-321; doi:10.1093/toxsci/kfn127
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Immunotoxic Effects of Perfluorononanoic Acid on BALB/c Mice
* Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, China
Graduate School of the Chinese Academy of Sciences, Beijing 100080, China
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, China
1 To whom correspondence should be addressed at Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. Fax: +86-10-64807099. E-mail: daijy{at}ioz.ac.cn.
Received May 7, 2008; accepted June 19, 2008
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Abstract |
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The effects of perfluorononanoic acid (PFNA) on the immune system and its mechanism of action in mice have not been elucidated. Thus, BALB/c mice were exposed to the PFNA (0, 1, 3, or 5 mg/kg/day) for fourteen days. Exposure to PFNA led to a decrease in body weight and in the weight of the lymphoid organs. Cell cycle arrest and apoptosis were observed in the spleen and thymus following PFNA exposure. In the thymus, PFNA mostly modulated CD4+CD8+ thymocytes, whereas the F4/80+, CD11c+, and CD49b+ cells were major targets in the spleen. Although concanavalin A–induced T lymphocyte blastogenesis was not altered by PFNA, production of interleukin (IL)-4 and interferon-gamma by splenic lymphocytes was remarkably impaired. The levels of cortisol and adrenocorticotrophic hormone in sera were increased; however, the expression of glucocorticoid receptor in the thymus was unchanged. In addition, expression of the peroxisome proliferator–activated receptors (PPAR-
and PPAR-
) and IL-1β were upregulated significantly in the thymus at a dose of 1 mg PFNA/kg/day. No significant changes in expression of the inhibitory protein I
B and IB kinase were observed. Together, these results suggest that PFNA exerts toxic effects on lymphoid organs and T cell and innate immune cell homeostasis in mice and that these effects may result from the activation of PPAR-, PPAR-, and the hypothalamic-pituitary-adrenal axis. Interestingly, at the transcriptional level, the nuclear factor-kappa B signaling pathway appears to be uninvolved in the immunotoxic potential of PFNA.
Key Words: PFNA; Immunotoxicity; PPAR; glucocorticoid; NF-B.
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