Role of interleukin-38 in regulating the expression of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor signal activation

Chen Jiawei; Xu Fang

doi:10.13406/j.cnki.cyxb.004112

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Role of interleukin-38 in regulating the expression of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor signal activation

Excellence in medical insights\：pathogenesis and clinical treatment of sepsis | 更新时间：2026-06-11

- Role of interleukin-38 in regulating the expression of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor signal activation
- Journal of Chongqing Medical University Vol. 51, Issue 6, Pages: 784-791(2026)
- 作者机构：
  
  重庆医科大学附属第一医院重症医学科，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.004112
  CLC： R392
- Received：25 December 2025，
  
  Revised：2026-03-31，
  
  Accepted：31 March 2026，
  
  Published：28 June 2026
- 稿件说明：
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陈佳伟，徐昉.IL-38对TCR信号活化后EL4细胞谷氨酰胺代谢网络调控酶基因表达的作用[J].重庆医科大学学报，2026，51（6）：784-791.

Chen Jiawei,Xu Fang.Role of interleukin-38 in regulating the expression of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor signal activation[J].Journal of Chongqing Medical University,2026,51(6):784-791.
陈佳伟，徐昉.IL-38对TCR信号活化后EL4细胞谷氨酰胺代谢网络调控酶基因表达的作用[J].重庆医科大学学报，2026，51（6）：784-791. DOI： 10.13406/j.cnki.cyxb.004112.

Chen Jiawei,Xu Fang.Role of interleukin-38 in regulating the expression of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor signal activation[J].Journal of Chongqing Medical University,2026,51(6):784-791. DOI： 10.13406/j.cnki.cyxb.004112.

摘要

目的

探究急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）时机体氨基酸代谢是否异常及白细胞介素38（interleukin 38，IL-38）对T细胞受体（T cell receptor，TCR）信号激活后EL4细胞谷氨酰胺代谢调控网络酶基因表达的作用。

方法

募集ARDS患者及重症监护病房（intensive care unit，ICU）对照患者各3例，对其血浆进行高通量靶标代谢组学检测，筛选差异代谢物并进行通路富集分析；采用分化抗原簇（cluster of differentiation，CD）3/CD28抗体刺激EL4细胞TCR信号通路，并以IL-38干预24 h，实时荧光定量逆转录聚合酶链式反应（real-time quantitative reverse transcription polymerase chain reaction，RT-qPCR）检测谷氨酰胺代谢网络核心酶基因的信使核糖核酸（messenger ribonucleic acid，mRNA）表达水平。

结果

在ARDS组患者血浆中鉴定出2-氧代苯丙氨酸、5-羟基赖氨酸、甲羟戊酸、2-羟基丁酸、L-胱氨酸、L-苯丙氨酸、3-甲基-2-氧代戊酸、L-缬氨酸、异亮氨酸等9种代谢物水平上调；IL-38干预组溶质载体家族1成员5（solute carrier family 1 member 5，

Slc1a5

）、谷氨酰胺合成酶（glutamine synthetase，

）、谷氨酸脱氢酶1（glutamate dehydrogenase 1，

Glud1

）、谷胱甘肽还原酶（Glutathione Reductase，

Gsr

）、谷氨酸-半胱氨酸连接酶调节亚基（glutamate-cysteine ligase modifier subunit，

Gclm

）、谷胱甘肽合成酶（glutathione synthetase，

Gss

）、异柠檬酸脱氢酶1（isocitrate dehydrogenase 1，

Idh1

）、谷胱甘肽过氧化物酶4（glutathione peroxidase 4，

Gpx4

）、十-十一易位甲基胞嘧啶双加氧酶1（Ten-Eleven Translocation 1，

Tet1

）的mRNA相对表达水平较对照组上调（

0.05）。IL-38干预组Gpx1表达较对照组降低（

0.05）。

结论

ARDS患者存在明显氨基酸代谢异常，IL-38参与调控TCR信号活化后EL4细胞的谷氨酰胺代谢。

Abstract

Objective

To investigate the presence or absence of abnormal amino acid metabolism in acute respiratory distress syndrome（ARDS），as well as the effect of interleukin-38（IL-38） on the expression levels of enzyme genes in the glutamine metabolic network of EL4 cells after T cell receptor（TCR） signal activation.

Methods

Three patients with ARDS and three patients admitted to the intensive care unit were enrolled，and high-throughput targeted metabolomics analysis was performed for their plasma samples to identify differentially expressed metabolites and conduct a pathway enrichment analysis. CD3/CD28 antibodies were used to stimulate the TCR signaling pathway of EL4 cells，followed by IL-38 intervention for 24 hours，and RT-qPCR was used to measure the mRNA expression levels of core enzyme genes in the glutamine metabolic network.

Results

In the ARDS group，nine metabolites were upregulated in plasma，i.e.，2-oxophenylalanine，5-hydroxylysine，mevalonic acid，2-hydroxybutyric acid，L-cystine，L-phenylalanine，3-methyl-2-oxovaleric acid，L-valine，and isoleucine. Compared with the control group，the IL-38 intervention group had significant increases in the relative mRNA expression levels of solute carrier family 1 member 5，glutamine synthetase，glutamate dehydrogenase 1，glutathione reductase，glutamate-cysteine ligase modifier subunit，glutathione synthetase，isocitrate dehydrogenase 1，glutathione peroxidase 1，glutathione peroxidase 4，and ten-eleven translocation 1（

0.05）.

Conclusion

Significant abnormalities in amino acid metabolism are observed in ARDS patients，and IL-38 participates in the regulation of glutamine metabolism in EL4 cells after TCR signal activation.

关键词

Keywords

references

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