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- Title
miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria.
- Authors
Barker, Kevin R.; Ziyue Lu; Hani Kim; Ying Zheng; Junmei Chen; Conroy, Andrea L.; Hawkes, Michael; Cheng, Henry S.; Njock, Makon-Sébastien; Fish, Jason E.; Harlan, John M.; López, Jose A.; Liles, W. Conrad; Kain, Kevin C.
- Abstract
miR-155 has been shown to participate in host response to infection and neuroinflammation via negative regulation of blood-brain barrier (BBB) integrity and T cell function. We hypothesized that miR-155 may contribute to the pathogenesis of cerebral malaria (CM). To test this hypothesis, we used a genetic approach to modulate miR-155 expression in an experimental model of cerebral malaria (ECM). In addition, an engineered endothelialized microvessel system and serum samples from Ugandan children with CM were used to examine anti-miR-155 as a potential adjunctive therapeutic for severe malaria. Despite higher parasitemia, survival was significantly improved in miR-155-/- mice versus wild-type littermate mice in ECM. Improved survival was associated with preservation of BBB integrity and reduced endothelial activation, despite increased levels of proinflammatory cytokines. Pretreatment with antagomir-155 reduced vascular leak induced by human CM sera in an ex vivo endothelial microvessel model. These data provide evidence supporting a mechanistic role for miR-155 in host response to malaria via regulation of endothelial activation, microvascular leak and BBB dysfunction in CM
- Subjects
INFLAMMATION; BLOOD-brain barrier disorders; CEREBRAL malaria; T cells; PARASITEMIA
- Publication
Molecular Medicine, 2017, Vol 23, p24
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2016.00139