AI Article Synopsis

  • Resolvins (Rvs) are natural lipid molecules that help resolve inflammation, which is crucial in diseases like sickle cell disease (SCD) that are marked by inflammation and blood flow problems.
  • A study using humanized SCD mice found that 17-resolvin D1 (17RvD1) effectively reduces inflammation and vascular issues by decreasing blood cell recruitment and neutrophil activity after hypoxia/reoxygenation events.
  • The protective effects of 17RvD1 are linked to enhancing the removal of dead cells, reducing pro-inflammatory signals, and blocking a key inflammatory pathway (NF-κB), suggesting it could be a new treatment for SCD's inflammation-related complications.

Article Abstract

Resolvins (Rvs), endogenous lipid mediators, play a key role in the resolution of inflammation. Sickle cell disease (SCD), a genetic disorder of hemoglobin, is characterized by inflammatory and vaso-occlusive pathologies. We document altered proresolving events following hypoxia/reperfusion in humanized SCD mice. We demonstrate novel protective actions of 17-resolvin D1 (17RvD1; 7, 8, 17-trihydroxy-4, 9, 11, 13, 15, 19-docosahexaenoic acid) in reducing ex vivo human SCD blood leukocyte recruitment by microvascular endothelial cells and in vivo neutrophil adhesion and transmigration. In SCD mice exposed to hypoxia/reoxygenation, oral administration of 17 RvD1 reduces systemic/local inflammation and vascular dysfunction in lung and kidney. The mechanism of action of 17-RvD1 involves (1) enhancement of SCD erythrocytes and polymorphonuclear leukocyte efferocytosis, (2) blunting of NF-κB activation, and (3) a reduction in inflammatory cytokines, vascular activation markers, and E-selectin expression. Thus, 17-RvD1 might represent a new therapeutic strategy for the inflammatory vasculopathy of SCD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337877PMC
http://dx.doi.org/10.1182/blood-2018-07-865378DOI Listing

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