Publication: Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production
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Issued Date
2013-06-28
Resource Type
ISSN
10902104
0006291X
0006291X
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2-s2.0-84879606891
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.436, No.2 (2013), 283-288
Suggested Citation
Aroonroong Suttitheptumrong, Sasiprapa Khunchai, Jutatip Panaampon, Umpa Yasamut, Atthapan Morchang, Chunya Puttikhunt, Sansanee Noisakran, Guy Haegeman, Pa thai Yenchitsomanus, Thawornchai Limjindaporn Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production. Biochemical and Biophysical Research Communications. Vol.436, No.2 (2013), 283-288. doi:10.1016/j.bbrc.2013.05.094 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/31290
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Title
Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production
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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.