Upregulation of proBDNF in the Mesenteric Lymph Nodes in Septic Mice
The immune status in the lymphatic system, especially mesenteric lymph nodes (MLNs), is critical to regulate the septic shock. Brain-derived neurotrophic factor (BDNF) in the enteric system has been reported to regulate enteric immunity. However, the role of its precursor, proBDNF, in the immune status of MLNs under sepsis condition is still unclear. This study aimed to characterize the expression pattern of proBDNF in MLNs after lipopolysaccharide (LPS) stimulation, and to investigate the association of pathogenesis of sepsis. LPS (20 mg/kg) was intraperitoneally injected to induce sepsis in mice. Survival curve analysis, routine blood tests, and liver and kidney function tests were performed to evaluate the severity of sepsis. QPCR and histological staining were performed to assess the mRNA levels of proinflammatory cytokines and degree of immune-inflammatory response in the MLNs. Furthermore, Western blotting, flow cytometry, and immunofluorescence were performed to examine the key molecules expression of proBDNF signaling. Intraperitoneal LPS injection significantly decreased the number of lymphocytes in blood but increased the number of T lymphocytes in MLNs. Serum alanine transaminase, aspartate transaminase, and blood urea nitrogen levels were increased in LPS-challenged mice compared to control mice. LPS administration upregulated proinflammatory cytokine gene expression and induced histological changes in the MLNs. LPS injection increased BDNF, proBDNF, and its receptor pan neutrophin receptor 75 (p75NTR) expression in MLNs. The increased proBDNF was mainly localized on CD3+ and CD4+ T cells in the medulla of MLNs. LPS-induced sepsis upregulated proBDNF expression in medulla T cells of MLNs. ProBDNF upregulation may be involved in the pathogenesis of septic shock.
KeywordsBrain-derived neurotrophic factor precursor Lipopolysaccharide Sepsis Mesenteric lymph nodes T cell
ZW conducted the study, data collection, data analysis, and manuscript preparation; JW and FZ conducted the study, data collection, and data analysis; YL helped to do the animals-related experiments; YY and JS helped with data analysis; HL and SW helped to design and analyze the data; XFZ provided reagents, data interpretation, and revised manuscripts; ZH and RD were responsible for design and interpretation of the work, data collection, data analysis, and manuscript drafting; all authors had a final approval of the manuscript submission.
This research was supported by National Natural Science Foundation of China (81771354 and to RD, 81873770 to LH), and the Hunan Province Science Foundation for Young Scientists of China (2018JJ3864 to SW).
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Conflict of Interest
The authors declare that they have no conflict of interest.
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