miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria
Kevin Richard Barker1,2, Ziyue Lu2, Hani Kim2
1Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Molecular Medicine (Cambridge, Mass.)
|February 10, 2017
Summary
MicroRNA-155 (miR-155) exacerbates cerebral malaria by disrupting blood-brain barrier integrity. Inhibiting miR-155 improved survival and protected the brain in experimental models, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- MicroRNA-155 (miR-155) plays a role in neuro-inflammation and host responses to infection.
- Its involvement in the pathogenesis of cerebral malaria (CM) is not fully understood.
Purpose of the Study:
- To investigate the role of miR-155 in experimental cerebral malaria (ECM).
- To evaluate anti-miR-155 as a potential adjunctive therapy for severe malaria.
Main Methods:
- Genetic modulation of miR-155 expression in a mouse model of ECM.
- Utilized an engineered endothelialized microvessel system and human CM serum samples.
- Assessed blood-brain barrier (BBB) integrity, endothelial activation, and survival rates.
Main Results:
- miR-155 knockout mice showed improved survival in ECM despite higher parasitemia.
- BBB integrity was preserved, and endothelial activation was reduced in miR-155 deficient mice.
- Antagomir-155 pre-treatment reduced serum-induced vascular leak in an ex vivo model.
Conclusions:
- miR-155 contributes mechanistically to CM pathogenesis by regulating endothelial activation and BBB dysfunction.
- Targeting miR-155 represents a potential therapeutic strategy for severe malaria.
