1. Academic Validation
  2. High-density lipoprotein reduces microglia activation and protects against experimental autoimmune encephalomyelitis in mice

High-density lipoprotein reduces microglia activation and protects against experimental autoimmune encephalomyelitis in mice

  • Int Immunopharmacol. 2022 Apr;105:108566. doi: 10.1016/j.intimp.2022.108566.
Shan Hong 1 Min Niu 2 Dongmei Meng 2 Aiqin Li 2 Qingzhe Dong 2 Jie Zhang 2 Xiaojun Tian 2 Shulai Lu 3 Yunlong Wang 4
Affiliations

Affiliations

  • 1 Affiliated Hospital of Qingdao University, Qingdao, China; Department of Pharmacology, Qingdao University, Qingdao, Shandong, China.
  • 2 Affiliated Hospital of Qingdao University, Qingdao, China.
  • 3 Stomatological Department, Qingdao Municipal Hospital, Qingdao, China. Electronic address: lshl97@163.com.
  • 4 Affiliated Hospital of Qingdao University, Qingdao, China; Department of Pharmacology, Qingdao University, Qingdao, Shandong, China. Electronic address: wylapollo@163.com.
Abstract

Studies have shown that high-density lipoprotein (HDL) is a powerful anti-atherosclerosis factor in vivo and in vitro, with anti-inflammatory effects, and it also plays an important role in the immune system and central nervous system (CNS). In this study, the BV2 microglia inflammation model and experimental autoimmune encephalomyelitis animal model were used to investigate the potential mechanism of HDL in multiple sclerosis. Our results show that HDL inhibits the activation of BV2 microglia in a model of BV2 microglia inflammation and were validated with primary microglia. HDL can down-regulate the expression of TNF-α, IL-6, iNOS and NO. Western blot results showed that HDL could reduce the expression levels of TLR4, CD14, MyD88 and NF-κB p65 LPS-induced microglia. In a mouse model of experimental autoimmune encephalomyelitis, hematoxylin-eosin (HE) staining showed decreased infiltration of inflammatory cells in brain and spinal cord tissues, and Luxol Fast Blue (LFB) staining showed significant improvement in spinal cord demyelination. We found that HDL reduced spinal cord and brain inflammation after EAE induction, inhibited the infiltration of CD68 and Iba-1 positive inflammatory cells, and reduced the production of multiple pro-inflammatory cytokines, including pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. Western blot showed that EAE mice HDL inhibited the activation of ERK1/2 and JNK in MAPK pathway and p-IκBα and P65 in NF-κB pathway. Taken together, our study suggests that HDL may influence microglia activation and inflammatory response in mice by regulating inflammatory signaling pathways, improving induction of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and provides further insights into HDL therapy for multiple sclerosis.

Keywords

Experimental autoimmune encephalomyelitis; High-density lipoprotein; Microglia; Multiple sclerosis.

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