Augmented miR-150 expression associated with depressed SOCS1 expression involved in dengue haemorrhagic fever

Abstract

Suppressors of cytokine signalling (SOCS) proteins regulate cytokine responses and control immune balance. The objective of our study was to determine whether the expression of SOCS1 and its potential regulatory microRNAs (miRNAs) in leukocytes is correlated to the development of dengue haemorrhagic fever (DHF). We performed a case-control study to investigate the SOCS1 and miRNA expression in leukocytes for patients with DF and DHF in a DENV-2 outbreak that occurred in Taiwan between 2002 and 2003. We performed reverse transcription polymerase chain reaction to evaluate the expression of SOCS1 and its regulatory miRNAs in mononuclear leukocytes obtained from patients with or without DHF. The reciprocal relationship between SOCS1 and miR-150 expression was validated in DENV-2-infected peripheral mononuclear cells (PBMCs). SOCS1 expression and lower IFN-γ level were significantly reduced in DHF patients, but not in patients with DF. Elevated SOCS1 and reduced miR-150 levels were detected 24h after DENV-2 infection in PBMCs. Transfection of a miR-150 mimic into CD14(+) cells infected with DENV-2 suppressed the induction of SOCS1 expression in a dose-dependent manner. We demonstrate for the first time that augmented miR-150 expression with depressed SOCS1 expression in CD14(+) cells are associated with the pathogenesis of DHF.