Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro.

Abstract

Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.

• Authors: Mo Yang, Li-Yue Li, Xiao-Di Qin, Xiao-Yan Ye, Shu Yu, Qing Bao, Lin Sun, Zhi-Bin Wang, Michael S Bloom, Pasi Jalava, Li-Wen Hu, Hong-Yao Yu, Xiao-Wen Zeng, Bo-Yi Yang, Guang-Hui Dong, Chun-Wei Li
• Journal: The Science of the total environment (Sci Total Environ) Vol. 766 Pg. 142365 (Apr 20 2021) ISSN: 1879-1026 [Electronic] Netherlands
• PMID: 33601665 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Alkanesulfonic Acids
• Caprylates
• Fluorocarbons
• perfluorooctanoic acid
• perfluorooctane sulfonic acid

Topics

• Alkanesulfonic Acids
• Animals
• Asthma (chemically induced)
• Caprylates
• Fluorocarbons (toxicity)
• Inflammation (chemically induced)
• Lung
• Mice
• Mice, Inbred BALB C