期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms241713265
关键词
NLRC5; microglia; NF-kappa B; neuroinflammation; depressive mouse model
NLRC5 plays a critical role in microglial activation and is associated with LPS or CUMS-induced depressive mouse models.
Microglia are believed to be the key immune effectors of the central immune microenvironment, and their dysregulation is associated with neuroinflammation and mood disorders. Nucleotidebinding oligomerization domain-like receptor family caspase recruitment domain-containing five (NLRC5) is a new member of the Nod-like receptor family. Recently, NLRC5 has been reported to be expressed by microglia. Nonetheless, the exact roles of NLRC5 in microglial activation and its function in depression have not been investigated yet. Herein, we found that reducing NLRC5 decreased lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) in primary cultured microglia and microglial cell lines but not in bone marrow-derived macrophages (BMDMs). In more detail, reducing NLRC5 diminished the secretion of LPS-induced cytokines by attenuating IKK alpha/beta phosphorylation and inhibiting NF-kappa B signaling. Moreover, the expression of Nlrc5 in the hippocampus of LPS- or chronic unpredictable mild stress (CUMS)-induced depressive mice was increased. In line with the in vitro findings, Nlrc5 deficiency inhibited microglial activation in the mouse hippocampus and improved LPS- or CUMS-induced depressive-like behaviors. In summary, we demonstrated the critical role of NLRC5 in LPS-induced microglial activation and LPS or CUMS-induced depressive mouse models.
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