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Title: Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production
Authors: Aroonroong Suttitheptumrong
Sasiprapa Khunchai
Jutatip Panaampon
Umpa Yasamut
Atthapan Morchang
Chunya Puttikhunt
Sansanee Noisakran
Guy Haegeman
Pa thai Yenchitsomanus
Thawornchai Limjindaporn
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 28-Jun-2013
Citation: Biochemical and Biophysical Research Communications. Vol.436, No.2 (2013), 283-288
Abstract: Dengue Virus (DENV) infection is an important mosquito-borne viral disease and its clinical symptoms range from a predominantly febrile disease, dengue fever (DF), to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Increased levels of cytokines - the so-called 'cytokine storm', contribute to the pathogenesis of DHF/DSS. In this study, we compared the expression of cytokine genes between mock-infected and DENV-infected HepG2 cells using a real-time PCR array and revealed several up-regulated chemokines and cytokines, including CXCL10 and TNF-α. Compound A (CpdA), a plant-derived phenyl aziridine precursor containing anti-inflammatory action and acting as a dissociated nonsteroidal glucocorticoid receptor modulator, was selected as a candidate agent to modulate secretion of DENV-induced cytokines. CpdA is not a glucocorticoid but has an anti-inflammatory effect with no metabolic side effects as steroidal ligands. CpdA significantly reduced DENV-induced CXCL10 and TNF-α secretion and decreased leukocyte migration indicating for the first time the therapeutic potential of CpdA in decreasing massive immune activation during DENV infection. © 2013 Elsevier Inc.
ISSN: 10902104
Appears in Collections:Scopus 2011-2015

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