Silencing Leukocyte Immunoglobulin-Like Receptor A1 in Monocytes Inhibits Inflammation in Mice with Multiple Sclerosis.

OBJECTIVE: Multiple sclerosis (MS), also called disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disorder in which the insulating covers of brain nerve cells and the spinal cord are impaired. Emerging evidence has highlighted leukocyte immunoglobulin-like receptor A1 (LILRA1) and its ability to suppress the secretion of various inflammatory factors.

METHOD: During this study, we explored cell viability, apoptosis, and levels of certain inflammatory factors when silencing LILRA1 in cultured spinal cord cells obtained from mice with MS. A mouse model of experimental autoimmune encephalomyelitis (EAE) was established. A vector system package was used to explore the function of LILRA1 in EAE. The damage of spinal cord tissues was observed by hematoxylin-eosin staining. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and flow cytometry were applied to detect cell viability, cell cycle distribution, and apoptosis. Enzyme-linked immunosorbent assay and Western blot analysis were adopted to detect the levels of interleukin (IL)-6, IL-17, and tumor necrosis factor-α (TNF-α) in the monocytes.

RESULTS: Mice with EAE exhibited highly expressed LILRA1, IL-6, IL-17, and TNF-α. LILRA1 silencing was shown to significantly decrease the cell viability and accelerate the cell apoptosis rate in mice with EAE. At the same time, downregulation of LILRA1 significantly decreased the mRNA and protein levels of IL-6, IL-17, and TNF-α in the mouse serum.

CONCLUSION: The key findings of this study collectively propose that LILRA1 suppression exerts a potent anti-inflammatory effect on MS mice. Overall, LILRA1 downregulation presents a promising therapeutic strategy for the treatment of MS.