Targeting Chemerin Receptor CMKLR1 in Multiple Sclerosis
Abstract
Therapies that target leukocyte trafficking pathways can reduce disease activity and improve clinical outcomes in multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is a widely studied animal model that shares many clinical and histological features with human MS. Chemokine-like receptor-1 (CMKLR1) is a chemoattractant receptor that is expressed by key effector cells in EAE and MS, including macrophages, subsets of dendritic cells, natural killer cells and microglia. CMKLR1-deficient mice develop less severe clinical and histological EAE than wild-type mice. In this study, we identified alphanaphthoyl ethyltrimethylammonium iodide (alpha-NETA) as a selective CMKLR1 small molecule antagonist that inhibits chemerin-triggered CMKLR1+ cell migration. Prophylactic dosing with alpha-NETA significantly delayed the onset of EAE induced in C57BL/6 mice. In addition, alpha-NETA treatment significantly inhibited accumulation of inflammatory leukocytes within the CNS. This study provides additional proof-of-concept data that targeting CMKLR1:chemerin interactions may be beneficial in preventing or treating MS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2012
- Accession Number
- ADA575594
Entities
People
- Brian Zabel
Organizations
- Palo Alto Veterans Institute for Research