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59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY'S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING, Athens, Greece, 14 - 17 September 2025, pp.324, (Summary Text)
The aim of this study is to investigate the effects of
perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on the
IL-17 signaling pathway, as well as
their relationship with the severity of Poly I:C-induced lung injury in
nine-week-old male Balb/c mice. A total of 11 groups were formed, each
comprising six nine-week-old male Balb/c mice. These included control groups
(sham, vehicle, intratracheal Poly I:C, and vehicle combined with intratracheal
Poly I:C), groups receiving PFOS+PFOA at doses of 1, 3, or 9 mg/kg/day to
assess baseline effects on IL-17 signaling, and groups receiving the same doses
in combination with Poly I:C to evaluate their impact on lung injury severity.
For the latter, Poly I:C was administered intratracheally following oral
exposure to PFOS+PFOA. The treatment solution was prepared by mixing PFOS and
PFOA at a 1:1 (w/w) ratio. Bronchoalveolar lavage fluid was analyzed to
quantify cytokine levels. The percentages of T helper (Th) lymphocyte subsets
were determined using flow cytometry. In addition, IL-17-related gene
expression in lung tissue was evaluated by RT-qPCR. Furthermore, lung samples
underwent histopathological evaluation to assess structural alterations
associated with inflammation and tissue damage. Poly I:C administration
significantly increased the percentages of Th17, Th1, and Th22 cells. This
increase was also observed in the combination groups, although the extent of
the increase was less pronounced compared to the Poly I:C group. Th2 cell
percentages showed a significant increase in the PFOS+PFOA groups, while no
significant changes were observed in Th9 cell percentages. RT-qPCR and cytokine
analyses confirmed the presence of immune response alterations in the lung
tissue. The observed increases in Th1 and Th17 cells
reflect the expected immunological activation by Poly I:C [1,2]. However, the
diminished responses in the combination groups modulate the immune system’s ability
to respond appropriately to such stimuli. While Th2 levels tended to decrease
in the Poly I:C group, the PFOS+PFOA-induced increase in Th2 cells may indicate
a shift toward an allergic or humoral-dominant immune profile [3,4]. The
activation of Th17 cells at both the flow cytometric and gene expression levels
suggests an imbalance that could contribute to mucosal inflammation [5,6].
Changes in Th22 cell populations also point to a potentially complex role in
tissue inflammation and repair dynamics. PFOS and PFOA are synthetic chemicals
to which humans are widely exposed, particularly through everyday items such as
cookware. Our findings suggest that these substances may disrupt pulmonary
immune responses under infection-like conditions. This immune dysregulation could
increase the risk of inappropriate inflammatory responses and tissue damage,
highlighting the importance of considering environmental toxicants in the
context of viral pandemics.
This work was supported by the
Scientific Research Projects Coordination Unit of Hacettepe University (Project
No: FUK-2022-20117). Eda Nur İnkaya is a recipient of the YÖK 100/2000 Ph.D.
Scholarship, funded by the Council of Higher Education (YÖK), Turkey.