title: Compound A, a dissociated glucocorticoid receptor modulator, reduces dengue virus-induced cytokine secretion and dengue virus production.
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.
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Aroonroong
authors.initials: A
authors.lastname: Suttitheptumrong
authors.forename: Sasiprapa
authors.initials: S
authors.lastname: Khunchai
authors.forename: Jutatip
authors.initials: J
authors.lastname: Panaampon
authors.forename: Umpa
authors.initials: U
authors.lastname: Yasamut
authors.forename: Atthapan
authors.initials: A
authors.lastname: Morchang
authors.forename: Chunya
authors.initials: C
authors.lastname: Puttikhunt
authors.forename: Sansanee
authors.initials: S
authors.lastname: Noisakran
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Thawornchai
authors.initials: T
authors.lastname: Limjindaporn
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D054441:Cell Migration Assays, Leukocyte; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003716:Dengue Virus / Q000254:growth & development* / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D010936:Plant Extracts / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031248:Salsola / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054357:Chemokine CXCL10; D016207:Cytokines; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D014439:Tyramine