Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1

American Journal of Neurodegenerative Disease

Antonio La Cava¹  James Sayre¹  Martina Wiedau-Pazos¹  Mathew T Mizwicki¹  Guanghao Liu¹  Michelle Mahanian¹  Larry Magpantay¹  Madhuri Chattopadhyay¹  Avi Siani¹  Milan Fiala¹ 

关键词: Amyotrophic lateral sclerosis (ALS);    superoxide dismutase 1 (SOD1);    interleukin-17A (IL-17A);    interleukin-6 (IL-6);    tumor necrosis factor-a;    docosahexaenoic acid (DHA);    resolvin D1 (RvD1);    inflammation;   

DOI  :  

学科分类：精神健康和精神病学

来源: e-Century Publishing Corporation

【 摘 要 】

Although the cause of neuronal degeneration in amyotrophic lateral sclerosis (ALS) remains hypothetical, there is evidence of spinal cord infiltration by macrophages and T cells. In post-mortem ALS spinal cords, 19.8 ± 4.8 % motor neurons, including caspase-negative and caspase-positive neurons, were ingested by IL-6- and TNF-α-positive macrophages. In ALS macrophages, in vitro aggregated superoxide dismutase-1 (SOD-1) stimulated in ALS macrophages expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, through activation of cyclooxygenase-2 (COX-2) and caspase-1. The lipid mediator resolvin D1 (RvD1) inhibited IL-6 and TNF-α production in ALS macrophages with 1,100 times greater potency than its parent molecule docosahexaenoic acid. ALS peripheral blood mononuclear cells (PBMCs) showed increased transcription of inflammatory cytokines and chemokines at baseline and after stimulation by aggregated wild-type SOD-1, and these cytokines were down regulated by RvD1. Thus the neurons are impacted by macrophages expressing inflammatory cytokines. RvD1 strongly inhibits in macrophages and PBMCs cytokine transcription but does not inhibit their production in PBMCs. Resolvins offer a new approach to ALS inflammation suppressing.

【 授权许可】

Unknown