Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides
Joint Authors
Chen, Guangxing
Shi, Xiaoyi
Lai, Chunhui
Zhao, Lianyu
Zhang, Mingying
Liu, Xi
Peng, Shanqin
Guo, Weizhong
Xu, Qiuying
Chen, Song
Source
Journal of Immunology Research
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-10
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
IL-37 is a cytokine that plays critical protective roles in many metabolic inflammatory diseases, and its therapeutic potential has been confirmed by exogenous IL-37 administration.
However, its regulatory mechanisms remain unclear.
U937 cells were treated with autophagy-modifying reagents (3-MA, chloroquine, and rapamycin) with or without LPS stimulation.
Thereafter, IL-37 expression and autophagic markers (Beclin1, P62/SQSTM1, and LC3) were determined.
For regulatory signal pathways, phosphorylated proteins of NF-κB (p65 and IκBα), AP-1 (c-Fos/c-Jun), and MAPK signal pathways (Erk1/2 and p38 MAPK) were quantified, and the agonists and antagonists of MAPK and NF-κB pathways were also used.
Healthy human peripheral blood mononuclear cells were treated similarly to confirm our results.
Four rhesus monkeys were also administered chloroquine to evaluate IL-37 induction in vivo and its bioactivity on CD4 proliferation and activation.
IL-37 was upregulated by rapamycin and chloroquine in both U937 cells and human PBMCs in the presence of LPS.
IL-37 was preferentially induced in autophagic cells associated with LC3 conversion.
AP-1 and p65 binding motifs could be deduced in the sequence of the IL-37 promoter.
Inductive IL-37 expression was accompanied with increased phosphorylated Erk1/2 and AP-1 and could be completely abolished by an Erk1/2 inhibitor or augmented by Erk1/2 agonists.
In monkeys, chloroquine increased IL-37 expression, which was inversely correlated with CD4 proliferation and phosphorylated STAT3.
IL-37 levels were induced by rapamycin and chloroquine through the LC3, Erk1/2, and NF-κB/AP-1 pathways.
Functional IL-37 could also be induced in vivo.
American Psychological Association (APA)
Shi, Xiaoyi& Lai, Chunhui& Zhao, Lianyu& Zhang, Mingying& Liu, Xi& Peng, Shanqin…[et al.]. 2020. Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides. Journal of Immunology Research،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1187377
Modern Language Association (MLA)
Shi, Xiaoyi…[et al.]. Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides. Journal of Immunology Research No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1187377
American Medical Association (AMA)
Shi, Xiaoyi& Lai, Chunhui& Zhao, Lianyu& Zhang, Mingying& Liu, Xi& Peng, Shanqin…[et al.]. Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides. Journal of Immunology Research. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1187377
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1187377