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

// Xiaojun Wen 1 , Lijiao Xiao 1 , Zhuoyan Zhong 2 , Limin Wang 3 , Ze Li 1 , Xiaoping Pan 1 and Zhonglin Liu 2,4 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.