Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production
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- 作者：Aroonroong Suttitheptumrong ; Sasiprapa Khunchai ; Jutatip Panaampon ; Umpa Yasamut ; Atthapan Morchang ; Chunya Puttikhunt ; Sansanee Noisakran ; Guy Haegeman ; Pa-thai Yenchitsomanus ; Thawornchai Limjindaporn
- 关键词：Dengue virus ; Dissociated glucocorticoid receptor modulator ; Compound A ; Dengue virus production ; Cytokine secretion
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2013
- 出版时间：28 June, 2013
- 年：2013
- 卷：436
- 期：2
- 页码：283-288
- 全文大小：1161 K
文摘
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-¦Á. 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-¦Á secretion and decreased leukocyte migration indicating for the first time the therapeutic potential of CpdA in decreasing massive immune activation during DENV infection.