scholarly journals Brain-Derived Neurotrophic Factor Suppressed Proinflammatory Cytokines Secretion and Enhanced MicroRNA(miR)-3168 Expression in Macrophages

2022 ◽  
Vol 23 (1) ◽  
pp. 570
Author(s):  
Hui-Chun Yu ◽  
Hsien-Bin Huang ◽  
Hsien-Yu Huang Tseng ◽  
Ming-Chi Lu
Keyword(s):  
Proinflammatory Cytokines ◽  
Neurotrophic Factor ◽  
Human Monocyte ◽  
Brain Derived Neurotrophic Factor ◽  
Neurotrophin Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
P75 Neurotrophin Receptor ◽  
Tnf Α ◽  
Potential Strategy ◽  
Cytokines Secretion

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)-1β, tumor necrosis factor (TNF)-α, and IL-6 in lipopolysaccharide (LPS)-stimulated macrophages but did not change their mRNA expression. BDNF suppressed IL-1β 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-1β, IL-6, and TNF-α 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.

scholarly journals Astrocytes Protect against Isoflurane Neurotoxicity by Buffering pro-brain–derived Neurotrophic Factor

2015 ◽  
Vol 123 (4) ◽  
pp. 810-819 ◽  
Author(s):  
Creed M. Stary ◽  
Xiaoyun Sun ◽  
Rona G. Giffard
Keyword(s):  
Cell Death ◽  
Neurotrophic Factor ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Derived Neurotrophic Factor ◽  
Neurotrophin Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neuronal Cultures ◽  
P75 Neurotrophin Receptor ◽  
Primary Neuronal Cultures

Abstract Background: Isoflurane induces cell death in neurons undergoing synaptogenesis via increased production of pro-brain–derived neurotrophic factor (proBDNF) and activation of postsynaptic p75 neurotrophin receptor (p75NTR). Astrocytes express p75NTR, but their role in neuronal p75NTR-mediated cell death remains unclear. The authors investigated whether astrocytes have the capacity to buffer increases in proBDNF and protect against isoflurane/p75NTR neurotoxicity. Methods: Cell death was assessed in day in vitro (DIV) 7 mouse primary neuronal cultures alone or in co-culture with age-matched or DIV 21 astrocytes with propidium iodide 24 h after 1 h exposure to 2% isoflurane or recombinant proBDNF. Astrocyte-targeted knockdown of p75NTR in co-culture was achieved with small-interfering RNA and astrocyte-specific transfection reagent and verified with immunofluorescence microscopy. proBDNF levels were assessed by enzyme-linked immunosorbent assay. Each experiment used six to eight replicate cultures/condition and was repeated at least three times. Results: Exposure to isoflurane significantly (P < 0.05) increased neuronal cell death in primary neuronal cultures (1.5 ± 0.7 fold, mean ± SD) but not in co-culture with DIV 7 (1.0 ± 0.5 fold) or DIV 21 astrocytes (1.2 ± 1.2 fold). Exogenous proBDNF dose dependently induced neuronal cell death in both primary neuronal and co-cultures, an effect enhanced by astrocyte p75NTR inhibition. Astrocyte-targeted p75NTR knockdown in co-cultures increased media proBDNF (1.2 ± 0.1 fold) and augmented isoflurane-induced neuronal cell death (3.8 ± 3.1 fold). Conclusions: The presence of astrocytes provides protection to growing neurons by buffering increased levels of proBDNF induced by isoflurane. These findings may hold clinical significance for the neonatal and injured brain where increased levels of proBDNF impair neurogenesis.

Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro–Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice*

2016 ◽  
Vol 44 (2) ◽  
pp. e70-e82 ◽  
Author(s):  
Anne Sebastiani ◽  
Matthias Granold ◽  
Anja Ditter ◽  
Philipp Sebastiani ◽  
Christina Gölz ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Adult Mice

scholarly journals Associations Between the Kynurenine Pathway, Proinflammatory Cytokines, and Brain-Derived Neurotrophic Factor in Hospitalized Patients With Chronic Schizophrenia: A Preliminary Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Naomichi Okamoto ◽  
Tomoya Natsuyama ◽  
Ryohei Igata ◽  
Yuki Konishi ◽  
Hirofumi Tesen ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Neurotrophic Factor ◽  
Psychiatric Symptoms ◽  
Chronic Schizophrenia ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Healthy Controls ◽  
Dsm 5 ◽  
Tnf Α ◽  
Healthy Control

Purpose: The kynurenine (Kyn) pathway may play a role in the pathophysiology of schizophrenia. This pathway shows crosstalk with proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and/or brain-derived neurotrophic factor (BDNF). Moreover, Kyn metabolites affect neurotransmission and cause neurotoxicity. To date, the influence of the Kyn pathway on proinflammatory cytokines and BDNF remains to be fully elucidated. The aim of this study was to investigate the relationships of the Kyn pathway with proinflammatory cytokines, BDNF, and psychiatric symptoms in patients with schizophrenia.Methods: Thirty patients with schizophrenia and ten healthy control participants were recruited for this study. All patients were diagnosed with schizophrenia using the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5). The healthy controls were those who did not fulfill any of the diagnostic criteria in the DSM-5. The serum levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF were measured in patients with schizophrenia and healthy controls. Patients with schizophrenia were also assessed for psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS).Results: Patients with schizophrenia and healthy controls showed no significant differences in the levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF. A significant positive correlation was found between the serum levels of TNF-α and Kyn (r = 0.53, p = 0.0026) and the Kyn/tryptophan (Trp) value (r = 0.67, p = 0.000046) in the schizophrenia group, but not in the healthy control group.Conclusion: TNF-α affects the Kyn pathway in patients with chronic schizophrenia, but not in the healthy individuals, although serum TNF-α levels showed no difference between the two groups. Associations between the Kyn pathway and the levels of proinflammatory cytokines and BDNF or psychotic symptoms might be complicated in hospitalized patients with chronic schizophrenia.

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