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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
  • View Affiliations / Copyright

    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
    Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 460
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    Published online on: March 3, 2021
       https://doi.org/10.3892/etm.2021.9891
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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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1 

Tsokos GC: Systemic lupus erythematosus. N Engl J Med. 365:2110–2121. 2011.PubMed/NCBI View Article : Google Scholar

2 

Kiriakidou M, Cotton D, Taichman D and Williams S: Systemic lupus erythematosus. Ann Intern Med. 159:ITC4–ITC1. 2013.PubMed/NCBI View Article : Google Scholar

3 

Sakaguchi S: Regulatory T cells: Key controllers of immunologic self-tolerance. Cell. 101:455–458. 2000.PubMed/NCBI View Article : Google Scholar

4 

Shevach EM: CD4+ CD25+ suppressor T cells: More questions than answers. Nat Rev Immunol. 2:389–400. 2002.PubMed/NCBI View Article : Google Scholar

5 

Sakaguchi S, Sakaguchi N, Asano M, Itoh M and Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 155:1151–1164. 1995.PubMed/NCBI

6 

Buckner JH: Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol. 10:849–859. 2010.PubMed/NCBI View Article : Google Scholar

7 

Mukai S, Ogawa Y, Urano F, Kudo-Saito C, Kawakami Y and Tsubota K: Novel Treatment of Chronic Graft-Versus-Host Disease in Mice Using the ER Stress Reducer 4-Phenylbutyric Acid. Sci Rep. 7(41939)2017.PubMed/NCBI View Article : Google Scholar

8 

Zeng M, Sang W, Chen S, Chen R, Zhang H, Xue F, Li Z, Liu Y, Gong Y, Zhang H, et al: 4-PBA inhibits LPS-induced inflammation through regulating ER stress and autophagy in acute lung injury models. Toxicol Lett. 271:26–37. 2017.PubMed/NCBI View Article : Google Scholar

9 

Mohammed-Ali Z, Lu C, Marway MK, Carlisle RE, Ask K, Lukic D, Krepinsky JC and Dickhout JG: Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria. Sci Rep. 7(41572)2017.PubMed/NCBI View Article : Google Scholar

10 

Zheng P, Lin Y, Wang F, Luo R, Zhang T, Hu S, Feng P, Liang X, Li C and Wang W: 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress. Am J Physiol Renal Physiol. 311:F763–F776. 2016.PubMed/NCBI View Article : Google Scholar

11 

Braakman I and Hebert DN: Protein folding in the endoplasmic reticulum. Cold Spring Harb Perspect Biol. 5(a013201)2013.PubMed/NCBI View Article : Google Scholar

12 

Fagone P and Jackowski S: Membrane phospholipid synthesis and endoplasmic reticulum function. J Lipid Res. 50 (Suppl):S311–S316. 2009.PubMed/NCBI View Article : Google Scholar

13 

Clapham DE: Calcium signaling. Cell. 131:1047–1058. 2007.PubMed/NCBI View Article : Google Scholar

14 

Bhandary B, Marahatta A, Kim HR and Chae HJ: An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. Int J Mol Sci. 14:434–456. 2012.PubMed/NCBI View Article : Google Scholar

15 

Lee AS: The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods. 35:373–381. 2005.PubMed/NCBI View Article : Google Scholar

16 

Lee WS, Sung MS, Lee EG, Yoo HG, Cheon YH, Chae HJ and Yoo WH: A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus. J Leukoc Biol. 97:425–433. 2015.PubMed/NCBI View Article : Google Scholar

17 

Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Görgün CZ and Hotamisligil GS: Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 313:1137–1140. 2006.PubMed/NCBI View Article : Google Scholar

18 

Kawasaki N, Asada R, Saito A, Kanemoto S and Imaizumi K: Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep. 2(799)2012.PubMed/NCBI View Article : Google Scholar

19 

Yokogawa M, Takaishi M, Nakajima K, Kamijima R, Fujimoto C, Kataoka S, Terada Y and Sano S: Epicutaneous application of toll-like receptor 7 agonists leads to systemic autoimmunity in wild-type mice: A new model of systemic lupus erythematosus. Arthritis Rheumatol. 66:694–706. 2014.PubMed/NCBI View Article : Google Scholar

20 

Hasham MG, Baxan N, Stuckey DJ, Branca J, Perkins B, Dent O, Duffy T, Hameed TS, Stella SE, Bellahcene M, et al: Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease. Dis Model Mech. 10:259–270. 2017.PubMed/NCBI View Article : Google Scholar

21 

Yan JJ, Lee JG, Jang JY, Koo TY, Ahn C and Yang J: IL-2/anti-IL-2 complexes ameliorate lupus nephritis by expansion of CD4+CD25+Foxp3+ regulatory T cells. Kidney Int. 91:603–615. 2017.PubMed/NCBI View Article : Google Scholar

22 

Lee YA, Kim HR, Lee JS, Jung HW, Kim HY, Lee GM, Lee J, Sim JH, Oh SJ, Chung DH, et al: CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome. PLoS One. 10(e0144549)2015.PubMed/NCBI View Article : Google Scholar

23 

Yu F, Haas M, Glassock R and Zhao MH: Redefining lupus nephritis: Clinical implications of pathophysiologic subtypes. Nat Rev Nephrol. 13:483–495. 2017.PubMed/NCBI View Article : Google Scholar

24 

Sakaguchi S: Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 22:531–562. 2004.PubMed/NCBI View Article : Google Scholar

25 

Masteller EL, Tang Q and Bluestone JA: Antigen-specific regulatory T cells - ex vivo expansion and therapeutic potential. Semin Immunol. 18:103–110. 2006.PubMed/NCBI View Article : Google Scholar

26 

Hasegawa H, Inoue A, Muraoka M, Yamanouchi J, Miyazaki T and Yasukawa M: Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice. Arthritis Res Ther. 9(R15)2007.PubMed/NCBI View Article : Google Scholar

27 

Weigert O, von Spee C, Undeutsch R, Kloke L, Humrich JY and Riemekasten G: CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice. Arthritis Res Ther. 15(R35)2013.PubMed/NCBI View Article : Google Scholar

28 

Lamarche C and Levings MK: Guiding regulatory T cells to the allograft. Curr Opin Organ Transplant. 23:106–113. 2018.PubMed/NCBI View Article : Google Scholar

29 

Ukena SN, Höpting M, Velaga S, Ivanyi P, Grosse J, Baron U, Ganser A and Franzke A: Isolation strategies of regulatory T cells for clinical trials: Phenotype, function, stability, and expansion capacity. Exp Hematol. 39:1152–1160. 2011.PubMed/NCBI View Article : Google Scholar

30 

Donnelly C, Dykstra B, Mondal N, Huang J, Kaskow BJ, Griffin R, Sackstein R and Baecher-Allan C: Optimizing human Treg immunotherapy by Treg subset selection and E-selectin ligand expression. Sci Rep. 8(420)2018.PubMed/NCBI View Article : Google Scholar

31 

Kim I, Xu W and Reed JC: Cell death and endoplasmic reticulum stress: Disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 7:1013–1030. 2008.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Choi Y, Jung J, Lee E, Kim K and Yoo W: 4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model. Exp Ther Med 21: 460, 2021.
APA
Choi, Y., Jung, J., Lee, E., Kim, K., & Yoo, W. (2021). 4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model. Experimental and Therapeutic Medicine, 21, 460. https://doi.org/10.3892/etm.2021.9891
MLA
Choi, Y., Jung, J., Lee, E., Kim, K., Yoo, W."4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model". Experimental and Therapeutic Medicine 21.5 (2021): 460.
Chicago
Choi, Y., Jung, J., Lee, E., Kim, K., Yoo, W."4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model". Experimental and Therapeutic Medicine 21, no. 5 (2021): 460. https://doi.org/10.3892/etm.2021.9891
Copy and paste a formatted citation
x
Spandidos Publications style
Choi Y, Jung J, Lee E, Kim K and Yoo W: 4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model. Exp Ther Med 21: 460, 2021.
APA
Choi, Y., Jung, J., Lee, E., Kim, K., & Yoo, W. (2021). 4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model. Experimental and Therapeutic Medicine, 21, 460. https://doi.org/10.3892/etm.2021.9891
MLA
Choi, Y., Jung, J., Lee, E., Kim, K., Yoo, W."4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model". Experimental and Therapeutic Medicine 21.5 (2021): 460.
Chicago
Choi, Y., Jung, J., Lee, E., Kim, K., Yoo, W."4‑phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model". Experimental and Therapeutic Medicine 21, no. 5 (2021): 460. https://doi.org/10.3892/etm.2021.9891
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