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苦参生物碱和皮质类固醇通过 Foxp3 基因表观遗传修饰协同提高哮喘 PBMC 中 IL-10/IL-5 比率
Authors Song Y, Wang ZZ, Wang L , Faybusovich P, Srivastava K, Liu C, Tversky J, Dunkin D, Busse P, Ren X , Miller R, Miao M, Li XM
Received 19 June 2021
Accepted for publication 12 October 2021
Published 23 December 2021 Volume 2021:14 Pages 1559—1571
DOI https://doi.org/10.2147/JAA.S321616
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Amrita Dosanjh
Background: It has been demonstrated that ASHMI (antiasthma-simplified herbal medicine intervention) can improve airway function and reduce inflammation in human asthmatic patients with high safety and tolerability. In addition, ASHMI significantly suppresses Th2 cytokine production and increases Th1 cytokine production in treating asthma.
Objective: Allergic asthma is associated with dysregulation of cytokines. We focused on IL-5 and IL-10 as signature Th2 and Treg cytokines to characterize ASHMI immunomodulatory components.
Methods: The effects of ASHMI and individual herbal constituents on IL-5 and IL-10 production by PBMCs from asthmatic subjects were determined ex vivo. Sophora flavescens (SF)-F2, containing alkaloid compounds, effects on PBMC IL-10 and IL-5 production in the presence or absence of dexamethasone (Dex), and on DNA methylation levels at the foxp3 gene promoter were determined.
Results: The ratio of anti-CD3/CD28 stimulated IL-10/IL-5 production by PBMCs from asthmatic subjects was significantly reduced compared to healthy subjects. In PBMCs from asthmatic subjects, ASHMI significantly reduced IL-5 production and increased IL-10 secretion in a dose-dependent manner (p < 0.05– 0.01). SF-F2 was most effective in increasing IL-10, whereas SF-F4 (flavonoid compounds) was most effective in suppressing IL-5 production. Dex-treated PBMCs from asthma subjects showed a trend of increasing ratio of IL-10/IL-5 while demonstrating reduced levels in both IL-5 and IL-10 (p < 0.05). Co-culture with Dex and SF-F2 significantly prevented Dex suppression of IL-10, while retained Dex-suppression of IL-5 production, and increased IL-10/IL-5 ratio by Dex. Co-culture with SF-F2 and Dex significantly reduced DNA methylation levels at the foxp3 gene promoter at CpG− 126.
Conclusion: The SF alkaloid-rich fraction may be responsible for ASHMI induction of IL-10 production by PBMCs and plays a synergistic effect with Dex for augmenting IL-10/IL-5 ratio.
Keywords: Sophora flavescens , IL-10/IL-5 ratio, asthma, foxp3 methylation, synergistic effect