Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Astaxanthin acts via LRP-1 to inhibit inflammation and reverse lipopolysaccharide-induced M1/M2 polarization of microglial cells

Xiaojun Wen, Lijiao Xiao, Zhuoyan Zhong, Limin Wang, Ze Li, Xiaoping Pan and Zhonglin Liu _

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Oncotarget. 2017; 8:69370-69385. https://doi.org/10.18632/oncotarget.20628

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Abstract

Xiaojun Wen1, Lijiao Xiao1, Zhuoyan Zhong2, Limin Wang3, Ze Li1, Xiaoping Pan1 and Zhonglin Liu2,4

1 Department of Neurology, Guangzhou First People’s Hospital, Guangzhou Medical University, The Second Affiliated Hospital, South China University of Technology, Guangzhou, China

2 Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

3 Department of Neurology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China

4 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China

Correspondence to:

Zhonglin Liu, email:

Xiaoping Pan, email:

Keywords: astaxanthin, M1/M2 phenotypes, low-density lipoprotein receptor-related protein 1, nuclear factor-κB, c-Jun N-terminal kinase, Gerotarget

Received: May 07, 2017 Accepted: August 17, 2017 Published: September 03, 2017

Abstract

Microglia become activated during neuroinflammation and produce neurotoxic and neurotrophic factors, depending on whether they acquire M1 proinflammatory or M2 anti-inflammatory phenotypes. Astaxanthin (ATX), a natural carotenoid, has anti-inflammatory and neuroprotective effects. We investigated whether ATX could reverse M1/M2 polarization and suppress neuroinflammation via low-density lipoprotein receptor-related protein-1 (LRP-1). We observed increased expression of M1 (TNF-α, IL-1β, and CD86) and decreased expression of M2 (Arg-1, IL-10, and CD206) markers in BV2 microglial cells stimulated with lipopolysaccharide (LPS). These alterations were reversed by pretreating the cells with ATX. Activation of the NF-κB and JNK pathways was observed upon LPS stimulation, which was reversed by ATX. ATX-induced M2 polarization was attenuated by inhibition of NF-κB and JNK. Pretreatment of LPS-stimulated BV2 cells with ATX resulted in increased LRP-1 expression. The addition of receptor-associated protein, an LRP-1 antagonist, ameliorated ATX-induced inactivation of NF-κB and JNK signaling, and M2 polarization. ATX promotes M2 polarization to suppress neuroinflammation via LRP-1 by inhibiting NF-κB and JNK signaling. This novel mechanism may suppress neuroinflammation in diseases such as Alzheimer’s disease.


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