Perfluoroalkyl Substances (PFASs) Decrease the Expression of Recombination-activating Genes (RAG1 and RAG2) in Human B Lymphoma Namalwa Cells

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 2022 Nov 3

PMID 36326898

Authors

Aafke W F Janssen

Jochem Louisse

Deborah Rijkers

Nicole E T Pinckaers

Sjoerdtje A Hoekstra

Ron L A P Hoogenboom

Ad A C M Peijnenburg

Karsten Beekmann

Affiliations

Soon will be listed here.

Abstract

Per- and polyfluoroalkyl substances (PFASs) are omnipresent and have been shown to induce a wide range of adverse effects, including hepatotoxicity, developmental toxicity and immunotoxicity. So far, little information is available about the mechanisms underlying the toxicity of PFASs, including those related to their immunotoxicity. Reported immunotoxic effects of PFASs include decreased antibody responses in experimental animals and humans, indicating that PFASs may, among others, affect B cell function. In the present study, we first assessed the effects of PFOA on the transcriptome of the human Namalwa B cell line using RNA seq analysis. Gene expression changes, analyzed using Ingenuity Pathway Analysis, pointed to various cellular processes affected by PFOA, including 'B cell development' and 'Primary immunodeficiency signaling'. Interestingly, PFOA decreased the expression of RAG1 and RAG2, genes involved in immunoglobulin and T cell receptor V(D)J recombination. As a next step, time- and concentration-dependent changes in the expression of RAG1 and RAG2 upon exposure to PFOA, PFNA, PFHxS and PFOS were studied through RT-qPCR analysis. Analysis with the concentration-response modeling software PROAST resulted in the following potency ranking: PFNA > PFOA > PFOS > PFHxS. Altogether, the present in vitro study provides insights into the effects of selected PFASs on B cells, identifying RAG1 and RAG2 expression as possible relevant targets that may play a role in the immunotoxicity of PFASs.

Citing Articles

Determination of immunotoxic potencies of a series of perfluoralkylsubstances (PFASs) in human Namalwa B lymphocyte and human Jurkat T lymphocyte cells.

Janssen A, Jansen Holleboom W, Rijkers D, Louisse J, Hoekstra S, Schild S Front Toxicol. 2024; 6:1347965.

PMID: 38549690 PMC: 10976438. DOI: 10.3389/ftox.2024.1347965.

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Pierzchalski A, Zenclussen A, Herberth G Front Immunol. 2024; 14:1327960.

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