Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms23010570
Keywords
BDNF; p75NTR; JNK; macrophages; proinflammatory cytokines; microRNAs
Funding
- Ministry of Science and Technology [MOST 110-2314-B-303-023]
- Buddhist Tzu Chi Medical Foundation [TCMF-A 108-05]
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The role of brain-derived neurotrophic factor (BDNF) and its signaling pathway in the production of proinflammatory cytokines in macrophages was investigated. BDNF suppressed the secretion of proinflammatory cytokines and the phosphorylation of JNK, while knockout of p75 neurotrophin receptor (p75NTR) suppressed the expression and secretion of proinflammatory cytokines. BDNF upregulated the expression of miR-3168.
We investigated the role of brain-derived neurotrophic factor (BDNF) and its signaling pathway in the proinflammatory cytokines production of macrophages. The effects of different concentrations of BDNF on proinflammatory cytokines expression and secretion in U937 cell-differentiated macrophages, and human monocyte-derived macrophages were analyzed using enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The CRISPR-Cas9 system was used to knockout p75 neurotrophin receptor (p75NTR), one of the BDNF receptors. Next-generation sequencing (NGS) was conducted to search for BDNF-regulated microRNA. A very low concentration of BDNF (1 ng/mL) could suppress the secretion of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6 in lipopolysaccharide (LPS)-stimulated macrophages but did not change their mRNA expression. BDNF suppressed IL-1 beta and IL-6 secretion in human monocyte-derived macrophages. In U937 cells, BDNF suppressed the phosphorylation of JNK and c-Jun. The p75NTR knockout strongly suppressed IL-1 beta, IL-6, and TNF-alpha secretion in macrophages and LPS-stimulated macrophages. BDNF regulated the expression of miR-3168 with Ras-related protein Rab-11A as its target. In conclusion, BDNF suppressed proinflammatory cytokines secretion in macrophages and inhibited the phosphorylation of JNK. Knockout of p75NTR suppressed proinflammatory cytokines expression and secretion. BDNF upregulated the expression of miR-3168. The inhibition of p75NTR could be a potential strategy to control inflammation.
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