Topoisomerase 2 inhibitor etoposide promotes interleukin-10 production in LPS-induced macrophages via upregulating transcription factor Maf and activating PI3K/Akt pathway.
Int Immunopharmacol
; 101(Pt A): 108264, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1487769
ABSTRACT
Topoisomerase (TOP) inhibitors were commonly used as chemotherapeutic agents in the treatment of cancers. In our present study, we found that etoposide (ETO), a topoisomerase 2 (TOP2) inhibitor, upregulated the production of Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-stimulated macrophages. Besides, other TOP2 inhibitors including doxorubicin hydrochloride (DOX) and teniposide (TEN) were also able to augment IL-10 production. Meanwhile, the expression levels of pro-inflammatory factors, for example IL-6 and TNF-α, were also decreased accordingly by the treatment of the TOP2 inhibitors. Of note, ETO facilitated IL-10 secretion, which might be regulated by transcription factor Maf via PI3K/AKT pathway, as pharmaceutic blockage of kinase PI3K or AKT attenuated ETO-induced Maf and IL-10 expression. Further, in LPS-induced mice sepsis model, the enhanced generation of IL-10 was observed in ETO-treated mice, whereas pro-inflammatory cytokines were decreased, which significantly reduced the mortality of mice from LPS-induced lethal cytokine storm. Taken together, these results indicated that ETO may exhibit an anti-inflammatory role by upregulating the alteration of transcription factor Maf and promoting subsequential IL-10 secretion via PI3K/Akt pathway in LPS-induced macrophages. Therefore, ETO may serve as a potential anti-inflammatory agent and employed to severe pro-inflammatory diseases including COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interleukin-10
/
Phosphatidylinositol 3-Kinases
/
Proto-Oncogene Proteins c-akt
/
Proto-Oncogene Proteins c-maf
/
Etoposide
/
Topoisomerase II Inhibitors
/
Anti-Inflammatory Agents
Limits:
Animals
Language:
English
Journal:
Int Immunopharmacol
Journal subject:
Allergy and Immunology
/
Pharmacology
Year:
2021
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS