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Hypoxia promotes lipopolysaccharide-induced CXCL10 expression in microglia

SHI Zi-Bi¹, HU Yue¹, RUAN Qian-Qian¹, FAN Ming¹, ZHAO Ming¹, ZHU Ling-Ling^1,2,3,4,*

¹Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China；²School of Life Sciences, Anhui Medical University, Hefei 230032, China；³Hengyang Medical School, University of South China, Hengyang 421001, China；⁴Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China

Abstract

This study was aimed to investigate the effect of hypoxia on lipopolysaccharide (LPS)-induced CXC-chemokine ligand-10 (CXCL10) expression and the underlying mechanism. C57BL/6J mice were randomly divided into control, hypoxia, LPS, and hypoxia combined with LPS groups. The LPS group was intraperitoneally injected with 0.5 mg/kg LPS, and the hypoxia group was placed in a hypobaric hypoxia chamber (simulated altitude of 6 000 m). The serum and hippocampal tissue samples were collected after 6 h of the treatment. The levels of CXCL10 in the serum and hippocampal tissue of mice were detected by ELISA. The microglia cell line BV2 and primary microglia were stimulated with hypoxia (1% O2) and/or LPS (100 ng/mL) for 6 h. The mRNA expression level of CXCL10 and its content in culture supernatant were detected by real-time quantitative PCR and ELISA, respectively. The phosphorylation levels of nuclear factor κB (NF-κB) signaling pathway-related proteins, p65 and IκBα, were detected by Western blot. Moreover, after NF-κB signaling pathway being blocked with a small molecular compound, PDTC, CXCL10 mRNA expression level was detected in the BV2 cells. The results showed that in the LPS-induced mouse inflammatory model, hypoxia treatment could promote LPS-induced up-regulation of CXCL10 in both serum and hippocampus. Compared with the cells treated with LPS alone, the expression of CXCL10 mRNA and the content of CXCL10 in the culture supernatant of BV2 cells treated with hypoxia combined with LPS were significantly increased. The CXCL10 mRNA level of primary microglial cells treated with hypoxia combined with LPS was significantly up-regulated. Compared with the cells treated with hypoxia or LPS alone, the phosphorylation levels of p65 and IκBα in the BV2 cells treated with hypoxia combined with LPS were significantly increased. PDTC blocked the induction of CXCL10 gene expression by LPS in the BV2 cells. These results suggest that hypoxia promotes LPS-induced expression of CXCL10 in both animal and cell models, and NF-κB signaling pathway plays an important role in this process.

Key words: lipopolysaccharide (LPS); hypoxia; microglia; CXC-chemokine ligand-10

Received: 　　Accepted:

Corresponding author: 朱玲玲　　E-mail: linglingzhuamms@126.com

DOI: 10.13294/j.aps.2022.0087

Citing This Article：

SHI Zi-Bi, HU Yue, RUAN Qian-Qian, FAN Ming, ZHAO Ming, ZHU Ling-Ling. Hypoxia promotes lipopolysaccharide-induced CXCL10 expression in microglia. Acta Physiol Sin 2023; 75 (2): 153-159 (in Chinese with English abstract).