Withaferin A Associated Differential Regulation of Inflammatory Cytokines

Frontiers in Immunology
Seema DubeyDev Karan

Abstract

A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA). Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β), CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB) in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsibl...Continue Reading

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Citations

Aug 20, 2019·The Journal of Pharmacology and Experimental Therapeutics·Daxesh P PatelFrank J Gonzalez
Apr 5, 2019·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Yibin LiuAunhua Jin
May 15, 2020·Environmental Science and Pollution Research International·Vishnu Sankar SivasankarapillaiDelia Mirela Tit
Feb 13, 2021·Cell Death & Disease·Yangliu XiaTingting Yan
Jan 24, 2020·European Journal of Medicinal Chemistry·Thadeu E M M CostaCarmen Penido
Mar 13, 2021·Frontiers in Pharmacology·Angela E PeterV Lakshmi Kalpana
May 21, 2021·Frontiers in Pharmacology·Akash SaggamBhushan Patwardhan
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nadire Özenver, Thomas Efferth
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rajib DasMohammad S Mubarak
Nov 25, 2021·Natural Product Reports·Gui-Yang XiaFeng Qiu

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Methods Mentioned

BETA
Profiler
PMA
X-ray
PCR
ELISA
enzyme-linked immunosorbent assay

Software Mentioned

Matrix Library
MatInspector
GraphPad Prism
ImaGene

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