Background/Aims: Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Methods: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. Results: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. Conclusion: Therefore, we suggest that microglial activation increases the synthesis of BDNF and that the release of BDNF can, in turn, activate microglia. A positive autocrine BDNF feedback loop from microglia may contribute to prolonged microglial activation.
Thousands of long noncoding RNAs (lncRNAs) have been reported and represent an important subset of pervasive genes associated with a broad range of biological functions. Abnormal expression levels of lncRNAs have been demonstrated in multiple types of human disease. However, the role of lncRNAs in systemic lupus erythematosus (SLE) remains poorly understood. In the present study, the expression patterns of lncRNAs and messenger RNAs (mRNAs) were investigated in peripheral blood mononuclear cells (PBMCs) in SLE using Human lncRNA Array v3.0 (8×60 K; Arraystar, Inc., Rockville, MD, USA). The microarray results indicated that 8,868 lncRNAs (3,657 upregulated and 5,211 downregulated) and 6,876 mRNAs (2,862 upregulated and 4,014 downregulated) were highly differentially expressed in SLE samples compared with the healthy group. Gene ontology (GO) analysis of lncRNA target prediction indicated the presence of 474 matched lncRNA-mRNA pairs for 293 differentially expressed lncRNAs (fold change, ≥3.0) and 381 differentially expressed mRNAs (fold change, ≥3.0). The most enriched pathways were ‘Transcriptional misregulation in cancer’ and ‘Valine, leucine and isoleucine degradation’. Furthermore, reverse transcription-quantitative polymerase chain reaction data verified six abnormal lncRNAs and mRNAs in SLE. The results indicate that the lncRNA expression profile in SLE was significantly changed. In addition, a range of SLE-associated lncRNAs were identified. Thus, the present results provide important insights regarding lncRNAs in the pathogenesis of SLE.
ObjectivesIt is well-known that lymphocytes play an important role in systemic lupus erythematosus (SLE). T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT) is one of immunosuppressive costimulatory molecules that mediates an inhibitory effect. However, its roles in SLE are poorly understood. This study was designed to investigate the correlation between the frequencies of TIGIT-expressing CD3+CD4+ T lymphocytes and SLE.MethodsPatients with SLE were recruited from the First Affiliated Hospital of Nanchang University. Medical history, clinical manifestations, physical examination and laboratory measurements were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were determined by flow cytometry. The frequencies of TIGIT-expressing CD3+CD4+ T lymphocytes in patients with SLE were further analyzed for correlations with markers of autoimmune response, inflammation, urine proteins and disease activity in SLE.ResultsThe frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was significantly elevated in SLE patients compared with healthy controls (P < 0.0001). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes in patients with SLE was increased significantly in subjects with high anti-dsDNA titer (P = 0.026), high anti-Sm titer (P = 0.026), and high levels of urine microalbumin (P = 0.046). Furthermore, The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was found to be positively correlated with the Disease Activity Index (SLEDAI) score in SLE (r2 = 0.082; P = 0.044).ConclusionIn SLE, the frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was elevated and associated with the disease activity.
In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.
Abnormal expression of long non-coding RNA (lncRNA) has been demonstrated to be involved in a variety of human diseases. However, the role of lncRNA remains largely unknown in rheumatoid arthritis (RA). The present study aimed to investigate whether lncRNA are differentially expressed in RA. Differentially expressed lncRNA and mRNA in peripheral blood mononuclear cells from individuals with RA and healthy controls were detected using a human lncRNA microarray containing 30,586 lncRNA and 26,109 coding transcripts. Several candidate lncRNA and mRNA in 24 paired samples were verified by reverse transcription-quantitative polymerase chain reaction analysis. Bioinformatics analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were used to evaluate signaling pathways and biological functions influenced by the differentially expressed mRNA. A total of 5,045 lncRNA (upregulated, 2,410; downregulated, 2,635) and 3,289 mRNA (upregulated, 1,403; downregulated, 1,886) were differentially expressed in patients with RA (fold change >2; P<0.05). The majority of abnormal lncRNA were from intergenic spacer regions (42%), natural antisense (19%) and intronic antisense (15%) to protein-coding loci. lncRNA target prediction indicated the presence of 135 potential lncRNA-mRNA target pairs for the 85 aberrant lncRNA and 109 aberrant mRNA. Significantly enriched (P<0.05) signaling pathways based on deregulated mRNA were mostly implicated in bile secretion, T cell receptor signaling pathway and systemic lupus erythematosus. In summary, to the best of our knowledge, the present study executed global expression profiling of lncRNA and mRNA involved in RA for the first time. These results may provide important insights regarding lncRNA in RA pathogenesis and provide potential therapeutic targets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.