Mechanism of immunosuppression in zebrafish (Danio rerio) spleen induced by environmentally relevant concentrations of perfluorooctanoic acid

Transcriptomic Analysis Reveals the Hepatotoxicity of Perfluorooctanoic Acid in Black-Spotted Frogs (Rana nigromaculata)

“…The decreased expression of TAP1 and TAP2 genes detected in this study indicated that immune function of the black-spotted frog is inhibited. In our previous study, we showed that PFOA resulted in immunosuppression in zebrafish, which aligns with the results of our present study [33]. Overall, these results indicate that PFOA exposure induces immunosuppression by downregulating the expression of immune-related genes, which further damages the immune system and causes immune disease such as primary immunodeficiency.…”

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

“…3x on day 9, 11 and 13)] In vitro: ↑ NF-κB (luciferase activity); ↑ degradation of I-κB and nuclear translocation of NF-κB; ↑ gene expression of pro-inflammatory cytokines; pre-treatment with a NF-κB inhibitor: ↓TNF-α production and luciferase activity; [ In vivo: allergic symptoms were ↑ by PFOS] [ 160 ] PFOS In vitro : rat primary KCs and hepatocytes treated with 100 μM PFOS for 48 hrs In vivo : male SD rats 1 or 10 mg/kg bw PFOS per gavage for 20 days; In vitro: KC cells - ↑ NF-κB activation and p65 translocation. ↑ I-κB and JNK phosphorylation in hepatocytes and KCs; ↑ production of TNF-α and IL-6 in KCs, and was ↓ by NF-kB inhibitor ↑ hepatocyte proliferation by altering regulatory proteins (↑ PCNA, c-Jun, c-MYC and CyD1 in vitro & in vivo) In vivo: hepatocellular damage and inflammation, ↑serum TNFα and IL-6 level [ 209 ] PFOA and PFOS In vitro : macrophages treated with six EDCs via sirtuin (SIRT) regulation using the murine macrophage RAW 264.7 cell line PFOS and PFOA did not alter NF-κB expression (only Mono(2-ethylhexyl) phthalate did) [ 210 ] PFOS In vivo (hepatotoxicity and immunotoxicity) in zebrafish: 0, 0.02, 0.04 and 0.08 mg/L of PFOS for 7, 14, and 21 days Immune-regulatory function in the liver was disturbed by affecting liver structure, enzyme activities (↓ACP, AKP, lysozyme, ↑MPO) via ↑ NF-κB signalling,↑ ROS [ 211 ] PFOA In vivo zebrafish ↑ TLR2/Myd88/p65 pathway → (↓ IFN and BAFF mRNA expression → ↓ of Ig secretion) lipid metabolism disorder enhances the immune toxicity level in the spleen [ 212 ] PFOS In vitro : mural BMDMs; human cells: THP-1 cells (10-200 nM PFOS according to the authors corresponding to PFOS-serum levels in most human subjects) [In vivo: wild type (WT) C57BL/6 J mice were injected i.p., acute: 5, 15, or 25 mg/kg/d for 5 days & chronic: 0.066 mg/kg/d for 30 days; OVA induced asthmatic exacerbation model] THP-1 cells: ↑ NF-κB signalling; Ca 2+ –PKC-dependent pathway; ↑mRNA levels and release of TNF-α and IL-6 BMDMs: ↑ phosphorylation of NF-κB p65 and degradation of IκBα [In vivo: PFOS induced inflammation, ↑ IL-6, TNF-α, IL-1ß) tissue damage (lungs, liver, kidneys) via activation of the AIM2 inflammasome; asthmatic exacerbation, ↑IL-4, IL-1ß] [ 158 ] PFOA In vivo : zebrafish were exposed to 0.05, 0.1, 0.5, and 1 mg/L for 21 days ↑TLR2 /Myd88/NF-κB (p65) pathway ↑ proinflammatory cytokines (IFN and IL-1β)...…”

A systematic evidence map of chronic inflammation and immunosuppression related to per- and polyfluoroalkyl substance (PFAS) exposure

“…Though data on toll-like receptor (TLR)-2 and -4 are also limited, PFOA exposure increased expression of mRNA related to the MyD88 pathway in zebrafish ( Zhong et al, 2020 ), and was also shown to upregulate the mRNA and protein levels of TLR-2 and 4 in gut, hepatic, and neuroinflammation in mice ( Shao et al, 2020 ; Shi et al, 2020 ). PFOA was also shown to increase enzyme and mRNA levels of cyclooxygenase-2 (COX-2), which is involved in the conversion of pro-inflammatory molecules, in both the liver and colon tissue of mice and in mast cells ( Shi et al, 2020 ; Singh et al, 2012 ; Yang et al, 2014 ).…”