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10.1016/j.intimp.2021.108264

http://scihub22266oqcxt.onion/10.1016/j.intimp.2021.108264
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suck abstract from ncbi


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pmid34715493      Int+Immunopharmacol 2021 ; 101 (Pt A): 108264
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  • Topoisomerase 2 inhibitor etoposide promotes interleukin-10 production in LPS-induced macrophages via upregulating transcription factor Maf and activating PI3K/Akt pathway #MMPMID34715493
  • Zhang J; Zhao H; Feng Y; Xu X; Yang Y; Zhang P; Lu Z; Zhang T
  • Int Immunopharmacol 2021[Dec]; 101 (Pt A): 108264 PMID34715493show ga
  • 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-alpha, 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.
  • |Animals[MESH]
  • |Anti-Inflammatory Agents/*pharmacology/therapeutic use[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Cell Line[MESH]
  • |Disease Models, Animal[MESH]
  • |Down-Regulation/drug effects[MESH]
  • |Etoposide/*pharmacology/therapeutic use[MESH]
  • |Female[MESH]
  • |Interleukin-10/genetics/*metabolism[MESH]
  • |Interleukin-6/genetics/metabolism[MESH]
  • |Lipopolysaccharides/toxicity[MESH]
  • |Macrophages/drug effects[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Phosphatidylinositol 3-Kinases/*metabolism[MESH]
  • |Proto-Oncogene Proteins c-akt/*metabolism[MESH]
  • |Proto-Oncogene Proteins c-maf/*genetics/metabolism[MESH]
  • |Shock, Septic/chemically induced/drug therapy[MESH]
  • |Topoisomerase II Inhibitors/*pharmacology/therapeutic use[MESH]
  • |Tumor Necrosis Factor-alpha/genetics/metabolism[MESH]


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