Dendritic cell (DC) can be stimulated by both exogenous
pathogen-associated molecular patterns (
PAMPs) such as
lipopolysaccharide (LPS) and endogenous damage-associated molecular patterns (DAMPs) such as high mobility group box-1
protein (
HMGB1).
MicroRNAs (
miRNAs) act as post-transcriptional fine tuners of
mRNA. Studies have focused mostly on the potential role of
miRNAs in DCs maturation triggered by
PAMPs, especially LPS, however, little is known about the regulatory mechanism underlying the effects of
miRNAs in DC maturation mediated by DAMPs, including
HMGB1. Here, we first profiled a
miRNA microarray of DCs stimulated by
HMGB1 and determined that the up-regulated
miRNA miR-181a-5p may act as a regulatory
miRNA in these cells. Computational algorithms predicted TNF-α
3'UTR to be targeted by miR-181a-5p, which was confirmed by the experiments involving
luciferase reporters. In addition, we found that TNF-α
mRNA was down-regulated by miR-181a-5p mimic, and significantly up-regulated by miR-181a-5p inhibitor. Taken together, we identified miR-181a-5p a negative regulator in HMGB1-induced immune responses by targeting TNF-α
mRNA in DCs. Moreover, we suggested that miR-181a-5p may play a role in regulating DC responses to
HMGB1 and serve as evidence indicating that novel
therapies targeting
miRNAs may be useful for treating immune dysfunction in the setting of
sepsis.