4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model

Choi,Yunjung; Jung,Ji-Hyun; Lee,Eun-Gyeong; Kim,Kyoung Min; Yoo,Wan-Hee

doi:10.3892/etm.2021.9891

4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model

Authors:
- Yunjung Choi
- Ji-Hyun Jung
- Eun-Gyeong Lee
- Kyoung Min Kim
- Wan-Hee Yoo
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Affiliations: Division of Rheumatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Jeollabukdo 54907, Republic of Korea, Research Institute of Clinical Medicine of Jeonbuk National University‑Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Jeollabukdo 54907, Republic of Korea
Published online on: March 3, 2021 https://doi.org/10.3892/etm.2021.9891
Article Number: 460
Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Impaired function of regulatory T cells (Tregs) contributes to the pathogenesis of systemic lupus erythematosus (SLE). Our previous study demonstrated aberrant responses of T lymphocytes to endoplasmic reticulum (ER) stress in patients with SLE. The present study investigated whether ER stress inhibition by 4‑phenylbutyric acid (4‑PBA) ameliorated lupus manifestations in an experimental lupus model and the effect of ER stress inhibition on the frequency and function of Tregs. A murine lupus model was induced through a 4‑week treatment with Resiquimod, a toll‑like receptor (TLR) 7 agonist. From the 8th week, the mice were treated with 4‑PBA for 4 weeks. 4‑PBA significantly decreased the levels of anti‑dsDNA antibodies and serum TNF‑α. A significant decrease in glomerulonephritis score was also observed in the 4‑PBA‑treated group. ER stress inhibition decreased the activated T and B lymphocytes population of splenocytes; however, the population of Tregs was not significantly different between the vehicle and 4‑PBA group. However, a markedly enhanced suppressive capacity of Treg was detected in the 4‑PBA‑treated group. The present results suggest that ER stress inhibition attenuated disease activity in an experimental model by improving the suppressive capacity of Tregs. Therefore, reduction of ER stress could be used as a beneficial therapeutic strategy in SLE.

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