全长白细胞介素-38（IL-38）在激活类风湿关节炎成纤维样滑膜细胞中是起促进还是抑制作用取决于白细胞介素-1β（IL-1β）。

Whether full-length IL-38 acts as a promoter or inhibitor in activating rheumatoid arthritis fibroblast-like synoviocytes depends on IL-1β.

机构信息

Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.

出版信息

Int J Rheum Dis. 2024 Jan;27(1):e15020. doi: 10.1111/1756-185X.15020.

DOI:10.1111/1756-185X.15020

PMID:38287552

Abstract

AIM

IL-38 is a recently discovered inflammatory factor that belongs to the IL-1 family and has full-length and truncated forms. Clinical findings demonstrated that serum IL-38 levels in people with infectious and autoimmune diseases are significantly different from those in healthy people, but the form remains unclear. We are keenly interested in learning more about the regulatory role of full-length IL-38 in rheumatoid arthritis (RA), a classic autoimmune disease.

METHODS

RA-fibroblast-like synoviocytes (RA-FLS) were isolated from six RA patients and stimulated with full-length IL-38 to observe IL-6 and IL-8 secretion. Then, the migration and invasion functions of FLS were assessed. Next, the protein expressions of the MAPK, NF-κB, and JAK pathways were evaluated. In addition, we examined the effect of full-length IL-38 on FLS functions in the presence of IL-1β. The function of FLS affected by full-length IL-38 was also examined after blocking IL-1 and IL-36 receptors.

RESULTS

The functions of FLS were activated after the cells were stimulated with full-length IL-38. IL-6 and IL-8 levels increased with an increase in the full-length IL-38 concentration, and full-length IL-38 induced the acceleration of FLS migration and invasion functions. In addition, the levels of proteins in the MAPK signaling pathway increased after stimulation with full-length IL-38 and depended on its concentration. However, when the FLS were stimulated by IL-38 and IL-1β simultaneously, all experiments generated opposite results. Full-length IL-38 inhibited FLS function in the presence of IL-1β. IL-1R and IL-36R blockers terminated all effects of full-length IL-38 on RA-FLS.

CONCLUSION

Full-length IL-38 activates FLS functions and acts as a promoter in RA, whereas it inhibits FLS functions and acts as an inhibitor of RA in the presence of IL-1β. The function of full-length IL-38 can be blocked by IL-1Ra and IL-36Ra.

摘要

目的

IL-38 是一种新发现的炎症因子，属于 IL-1 家族，具有全长和截短形式。临床研究发现，感染性和自身免疫性疾病患者的血清 IL-38 水平与健康人有显著差异，但具体形式尚不清楚。我们非常感兴趣的是，深入了解全长 IL-38 在类风湿关节炎（RA）中的调控作用，RA 是一种经典的自身免疫性疾病。

方法

从 6 例 RA 患者中分离 RA 成纤维样滑膜细胞（RA-FLS），用全长 IL-38 刺激，观察 IL-6 和 IL-8 的分泌。然后评估 FLS 的迁移和侵袭功能。接下来，评估 MAPK、NF-κB 和 JAK 通路的蛋白表达。此外，我们还研究了全长 IL-38 在存在 IL-1β 时对 FLS 功能的影响。在阻断 IL-1 和 IL-36 受体后，还检测了全长 IL-38 对 FLS 功能的影响。

结果

全长 IL-38 刺激细胞后，FLS 功能被激活。随着全长 IL-38 浓度的增加，IL-6 和 IL-8 水平增加，全长 IL-38 诱导 FLS 迁移和侵袭功能的加速。此外，全长 IL-38 刺激后 MAPK 信号通路蛋白水平增加，且依赖于其浓度。然而，当 FLS 同时受到 IL-38 和 IL-1β 的刺激时，所有实验都产生了相反的结果。在存在 IL-1β 的情况下，全长 IL-38 抑制 FLS 功能。IL-1R 和 IL-36R 阻滞剂终止了全长 IL-38 对 RA-FLS 的所有作用。