Tumor necrosis factor-α-induced protein 8-like 2 alleviates morphine antinociceptive tolerance through reduction of ROS-mediated apoptosis and MAPK/NF-κB signaling pathways

Yang, Zhongxue; Zhang, Feifei; Mannan, Abdul; Jiang, Jinhong; Li, Yanqiang; Li, Yeqi; Chen, Yin; Xing, Yanhong; Liu, Su; Chen, Lu

doi:10.1016/j.neuropharm.2023.109667

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…The increased levels of B-cell activating factor (BAFF) are a consequence of both acute and chronic inflammation ( Matharu et al, 2013 ). Research findings indicate that the inhibition of the TLR4/NF-κB signaling pathway can effectively suppress microglia activation and neuroinflammatory responses, leading to an improved analgesic effect of morphine ( Yang et al, 2023 ). HLA-DR, a cell surface receptor belonging to the MHC class II family, is encoded by the human leukocyte antigen complex located in chromosome 6 region 6P21.…”

Section: Discussionmentioning

confidence: 99%

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Han,

Gao,

Wang

et al. 2024

Front. Microbiol.

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BackgroundPrevious researches have suggested a significant connection between the gut microbiota/immune cells and morphine tolerance (MT), but there is still uncertainty regarding their causal relationship. Hence, our objective is to inverstigate this causal association and reveal the impact of gut microbiota/immune cells on the risk of developing MT using a two-sample Mendelian randomization (MR) study.MethodsWe conducted a comprehensive analysis using genome-wide association study (GWAS) summary statistics for gut microbiota, immune cells, and MT. The main approach employed was the inverse variance-weighted (IVW) method in MR. To assess horizontal pleiotropy and remove outlier single-nucleotide polymorphisms (SNPs), we utilized the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique as well as MR-Egger regression. Heterogeneity detection was performed using Cochran’s Q-test. Additionally, leave-one-out analysis was carried out to determine if any single SNP drove the causal association signals. Finally, we conducted a reverse MR to evaluate the potential of reverse causation.ResultsWe discovered that 6 gut microbial taxa and 16 immune cells were causally related to MT (p < 0.05). Among them, 2 bacterial features and 9 immunophenotypes retained a strong causal relationship with lower risk of MT: genus. Lachnospiraceae NK4A136group (OR: 0.962, 95% CI: 0.940–0.987, p = 0.030), genus. RuminococcaceaeUCG011 (OR: 0.960, 95% CI: 0.946–0.976, p = 0.003), BAFF-R on B cell (OR: 0.972, 95% CI: 0.947–0.998, p = 0.013). Furthermore, 4 bacterial features and 7 immunophenotypes were identified to be significantly associated with MT risk: genus. Flavonifractor (OR: 1.044, 95% CI: 1.017–1.069, p = 0.029), genus. Prevotella9 (OR: 1.054, 95% CI: 1.020–1.090, p = 0.037), B cell % CD3-lymphocyte (OR: 1.976, 95% CI: 1.027–1.129, p = 0.026). The Cochrane’s Q test revealed no heterogeneity (p > 0.05). Furthermore, the MR-Egger and MR-PRESSO analyses reveal no instances of horizontal pleiotropy (p > 0.05). Besides, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the gut microbial taxa and immune cells exposure-outcome effect were attenuated.ConclusionOur research confirm the potential link between gut microbiota and immune cells with MT, shedding light on the mechanism by which gut microbiota and immune cells may contribute to MT. These findings lay the groundwork for future investigations into targeted prevention strategies.

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Section: Discussionmentioning

confidence: 99%

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Han,

Gao,

Wang

et al. 2024

Front. Microbiol.

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“…The activation of the MAPK and NF-κB signaling pathways by morphine has been confirmed by numerous studies (Ji et al, 2020;Ren et al, 2022;Ahmadi et al, 2023;Yang et al, 2023). However, the role of Toll-like receptor 4 (TLR4) in this process remains highly controversial (Eisenstein, 2019;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 97%

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Chen,

Liu,

Huang

2024

Front. Pharmacol.

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BackgroundThe effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action.MethodsBy repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4+ T cells and CD8+ T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered.ResultsRepeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4+ T cells, with little effect on CD8+ T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees.ConclusionRepeated intraperitoneal injection of oxycodone induces immunosuppression in mice.

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Endogenous opiates and behavior: 2023

Bodnar

2024

Peptides

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Tumor necrosis factor-α-induced protein 8-like 2 alleviates morphine antinociceptive tolerance through reduction of ROS-mediated apoptosis and MAPK/NF-κB signaling pathways

Cited by 4 publications

References 38 publications

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Endogenous opiates and behavior: 2023

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