The Long Non-coding RNA NEAT1/miR-224-5p/IL-33 Axis Modulates Macrophage M2a Polarization and A1 Astrocyte Activation

• Published in: Molecular neurobiology Vol. 58; no. 9; pp. 4506 - 4519
• Main Authors: Liu, Dongliang, Wei, Yuehua, Liu, Yudong, Wu, Tianding, Hu, Jianzhong, Lu, Hongbin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-09-2021; Springer Nature B.V
• Subjects: Animals; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell activation; Cell Biology; Cell Polarity; Interleukin 13; Interleukin 4; Interleukin-33 - metabolism; Kinases; Leukocytes (mononuclear); Macrophage Activation; Macrophages; Macrophages - cytology; Macrophages - metabolism; Mice; MicroRNAs - metabolism; Neurobiology; Neurology; Neurosciences; Non-coding RNA; Polarization; Proteins; RNA, Long Noncoding - metabolism; Signal Transduction - physiology; miR-224-5p; Macrophage polarization; IL-33; Long non-coding RNA NEAT1; A1 astrocyte activation
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-021-02405-x

To identify potential regulators and investigate the molecular mechanism of macrophage polarization affecting astrocyte activation from the perspective of non-coding RNA regulation, we isolated mouse bone marrow mononuclear cells (BMMNCs)–induced macrophages toward M1 or M2a polarization. Long non-coding RNA NEAT1 and IL-33 expression levels were significantly upregulated in M2a macrophages; NEAT1 knockdown in M2a macrophages markedly reduced the protein levels of IL-33 and M2a markers, IL-4 and IL-13 concentrations, and the bacterial killing capacity of M2a macrophages. NEAT1 acted as a competing endogenous RNA (ceRNA) to regulate IL-33 expression by sponging miR-224-5p in M2a macrophages; NEAT1 knockdown upregulated miR-224-5p expression, while miR-224-5p inhibition increased the protein content and concentration of IL-33. miR-224-5p inhibition exerted the opposite effects on the protein levels of IL-33 and M2a markers, IL-4 and IL-13 concentrations, and the bacterial killing capacity of M2a macrophages compared to NEAT1 knockdown; the effects of NEAT1 knockdown were significantly reversed by miR-224-5p inhibition. M2a macrophage conditioned medium (CM) significantly suppressed the activation of A1 astrocytes. NEAT1 knockdown M2a macrophage CM led to enhanced A1 astrocyte activation while miR-224-5p–silenced M2a macrophage CM led to a blockade of A1 astrocyte activation; the effects of NEAT1 knockdown M2a macrophage CM on A1 astrocyte activation were significantly reversed by miR-224-5p inhibition in M2a macrophages. The NEAT1/miR-224-5p/IL-33 axis modulates macrophage M2a polarization, therefore affecting A1 astrocyte activation.