Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model.
MicroRNAs (miRs) regulate immunological pathways in health and disease, and a number of miRs have been shown to be altered in mouse models of asthma. The secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to be defective in many inflammatory diseases including asthma. We recently demonstrated that miR-106a inhibits IL-10 in a post-transcriptional manner. In this study, we investigated the effect of inhibition of mmu-miR106a in asthmatic condition to find its possible role as a therapeutic target. Our in vitro experiments with mouse macrophage, RAW264.7, revealed that mmu-miR-106a potentially decreased IL-10 along with increase in proinflammatory cytokine. Furthermore, administration of mmu-miR-106a to naive mice reduced IL-10 levels in lungs in a dose-dependent manner without altering lung histology. Most interestingly, knockdown of mmu-miR-106a in an established allergic airway inflammation has significantly alleviated most of the features of asthma such as airway hyperresponsiveness, airway inflammation, increased Th2 response, goblet cell metaplasia, and subepithelial fibrosis along with increase in IL-10 levels in lung. This represents the first in vivo proof of a miRNA-mediated regulation of IL-10 with a potential to reverse an established asthmatic condition.
Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Amit
A
Sharma
Manish
M
Kumar
Tanveer
T
Ahmad
Ulaganathan
U
Mabalirajan
Jyotirmoi
J
Aich
Anurag
A
Agrawal
Balaram
B
Ghosh
D000818:Animals; D001249:Asthma / Q000628:therapy*; D002460:Cell Line; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*
C556062:IL10 protein, mouse; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D016753:Interleukin-10