IL-37 counteracts inflammatory injury in the temporomandibular joint via the intracellular pathway

Jun Li; Sisi Peng; Ying Yan; Shan Yan; Xin Cao; Yong Li; Luying Zhu; Jie Xu

doi:10.3389/fphar.2023.1250216

IL-37 counteracts inflammatory injury in the temporomandibular joint via the intracellular pathway

Front Pharmacol. 2023 Nov 20:14:1250216. doi: 10.3389/fphar.2023.1250216. eCollection 2023.

Authors

Jun Li^#^{1

2

3

4

5}, Sisi Peng^#^{1

2

3}, Ying Yan^{1

2

3}, Shan Yan^{1

2

3}, Xin Cao^{1

2

3}, Yong Li^{1

2

3}, Luying Zhu^{1

2

3}, Jie Xu^{1

2

3}

Affiliations

¹ College of Stomatology, Chongqing Medical University, Chongqing, China.
² Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China.
³ Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
⁴ Chongqing Emergency Medical Center, Chongqing, China.
⁵ Chongqing University Central Hospital, Chongqing, China.

^# Contributed equally.

Abstract

Background: The temporomandibular joint is often afflicted by osteoarthritis (TMJOA), causing pain and dysfunction, which is particularly prevalent in the elderly population. IL-37 is effective in avoiding excessive inflammatory damage to the organism. This article investigates the role and mechanism of intracellular IL-37 in TMJOA. Methods: Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blotting, Senescence-associated β-galactosidase staining, immunofluorescence, and lentivirus were performed to elucidate the underlying mechanism. Results: The results confirmed that IL-37 in synovial cells decreased with aging. Inflammatory stimulus elevated intracellular IL-37 in synoviocytes, while lentiviral knockdown of IL-37 resulted in more inflammatory factor production. Dynamic changes of IL-37 were observed in the nucleus and supernatant. In addition, Caspease-1 inhibitor hindered intracellular IL-37 maturation, and Smad3 inhibitor caused the loss of nuclear translocation of mature IL-37. Transfection of synovial cells with IL-37-expressing lentivirus resulted in relief not only of synovitis but also of the cartilage damage and inflammation caused by synovitis. Conclusion: This study provides new insights into the intracellular anti-inflammatory mechanism of IL-37. It also confirms that IL-37 decreases with cellular senescence and that increasing intracellular IL-37 can effectively treat synovitis and synovitis-induced inflammatory damage to cartilage.

Keywords: inflammation; intracellular IL-37; osteoarthritis; synovitis; temporomandibular joint.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81800999 to JX), the Chongqing Health Commission and Science and Technology Bureau Foundation (2023ZDXM019 to JX).