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The toxicity of perfluorodecanoic acid is mainly manifested as a deflected immune function

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Abstract

Background

Perfluorodecanoic acid (PFDA) is a type of perfluoroalkyl acid (PFAA). PFDA has toxicity similar to dioxin; its effect on the body is not through a single target or a single pathway. However, the mechanism at the global level is still unclear.

Methods and Results

We treated mice with PFDA and characterized the global changes in gene expression in the liver using microarray analyses. The enriched KEGG pathways and GO analyses revealed that PFDA greatly affected the immune response, which was different from the response of gastric cells previously studied. As a proof of principle, the expressions of IL-1β and IL-18 were both decreased after PFDA treatment, and qRT-PCR and ELISAs verified the reduction of IL-1β and IL-18 in liver tissues. Mechanistic investigations indicated that PFDA inhibited caspase-1 activation, and decreased the mRNA levels of NLRP1, NLRP3, and NLRC4; thus, suggesting that inflammasome assemblies were suppressed. Further microarray data revealed that cIAP2 and its binding proteins, which are critical for regulating inflammasome assembly, were also repressed by PFDA. In addition, flow cytometry results revealed a significant inhibition of Th1 cell differentiation in the livers of PFDA-treated mice.

Conclusions

The results of this study suggested that one of the main toxic effects of PFDA on livers was the inhibition of immune response.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PFDA:

Perfluorodecanoic acid

qRT-PCR:

Quantitative reverse transcriptase-polymerase chain reaction

KEGG:

Kyoto encyclopedia of genes and genomes

NLRP:

NLR family pyrin domain containing 1

NNMT:

Nicotinamide N-methyltransferase

FABP1:

Fatty acid binding protein 1

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

PPARα:

Peroxisome proliferator-activated receptor α

TCDD:

2,3,7,8-Tetrachlorodibenzo-p-dioxin

DAVID:

Database annotations, visualization and comprehensive discovery

NLRC4:

NLR family CARD domain containing 4

PMA:

Propylene glycol methyl ether acetate

cIAP2:

Cellular inhibitor of apoptosis 2

SCD3:

Stearoyl-coenzyme A desaturase 3

OLR1:

Oxidized low density lipoprotein receptor 1

ACSL:

Acyl-CoA synthetase long chain family member 1

ASC:

Apoptosis-related speck-like protein containing a CARD

Birc3:

Baculoviral IAP repeat containing 3

PFAAs:

Perfluoroalkyl acids

CPT:

Carnitine palmitoyltransferase

TRAF:

TNF receptor-associated factor

GO:

Gene Ontology

Th1:

T helper cell type 1

TLR:

Toll-like receptor

ANGPTL4:

Angiopoietin like 4

DMSO:

Dimethyl sulfoxide

TNF:

Tumor necrosis factor

ELISA:

Enzyme-linked immunosorbent assay

SDS:

Sodium dodecyl sulfate

PBS:

Phosphate buffer saline

FBS:

Fetal bovine serum

CYP:

Cytochrome P450

APOA2:

Apolipoprotein A2

BFA:

Brefeldin A

ACOX1:

Acyl-coenzyme A oxidase 1

MMP1:

Matrix metallopeptidase 1

PFAAs:

Perfluoroalkyl acids

CPT:

Carnitine palmitoyltransferase

TRAF:

TNF receptor-associated factor

GO:

Gene Ontology

Th1:

T helper cell type 1

TLR:

Toll-like receptor

ANGPTL4:

Angiopoietin like 4

DMSO:

Dimethyl sulfoxide

TNF:

Tumor necrosis factor

ELISA:

Enzyme-linked immunosorbent assay

SDS:

Sodium dodecyl sulfate

PBS:

Phosphate buffer saline

FBS:

Fetal bovine serum

CYPCYP:

Cytochrome P450

APOA2:

Apolipoprotein A2

BFA:

Brefeldin ABrefeldin A

ACOX1:

Acyl-coenzyme A oxidase 1Acyl-coenzyme A oxidase 1

MMP1:

Matrix metallopeptidase 1

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Acknowledgements

The study was supported by The Open Research Fund of State Key Laboratory of Environmental Chemistry and Ecotoxicology (KF2014-08), and Shandong provincial natural science foundation, China (ZR2020QH220).

Funding

The study was supported by The Open Research Fund of State Key Laboratory of Environmental Chemistry and Ecotoxicology (KF2014-08), and Shandong provincial natural science foundation, China (ZR2020QH220).

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Author notes

  1. Keming Li, Qian Zhao, Ziyan Fan have contributed equally to this wor

Authors and Affiliations

  1. Department of Medical Microbiology, School of Basic Medical Science & Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Keming Li, Qian Zhao, Shouyin Jia & Shili Liu

  2. Shandong Academy of Chinese Medicine, No. 7 Yanzishanxi Road, Jinan, 250013, Shandong, China

    Keming Li

  3. China National Tobacco Quality Supervision and Test Center, Zhengzhou, 450001, Henan, China

    Ziyan Fan

  4. Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China

    Qing Liu

  5. The Second Hospital of Shandong University, Jinan, 250012, Shandong, China

    Fengyan Liu

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  1. Keming Li
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Contributions

SL designed the research and prepared the manuscript; KL, QZ, ZF, SJ and FL performed the experiments and prepared the figures; QL provided testing equipment and assisted in testing.

Corresponding author

Correspondence to Shili Liu.

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The mouse experiment of this work was approved by the Ethics Committee of School of Basic Medical Science, Shandong University, Jinan, China (ECSBMSSDU2019-2-70).

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Li, K., Zhao, Q., Fan, Z. et al. The toxicity of perfluorodecanoic acid is mainly manifested as a deflected immune function. Mol Biol Rep 49, 4365–4376 (2022). https://doi.org/10.1007/s11033-022-07272-w

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