Ulcerative colitis(UC)is a chronic and non-specific inflammatory bowel disease(IBD).Huanglian Ganjiang decoction(HGD),derived from ancient book Beiji Qianjin Yao Fang,has demonstrated efficacy in treating UC patients ...Ulcerative colitis(UC)is a chronic and non-specific inflammatory bowel disease(IBD).Huanglian Ganjiang decoction(HGD),derived from ancient book Beiji Qianjin Yao Fang,has demonstrated efficacy in treating UC patients traditionally.Previous research established that the compatibility of cold herb Coptidis Rhizoma+Phellodendri Chinensis Cortex(CP)and hot herb Angelicae Sinensis Radix+Zingiberis Rhizoma(AZ)in HGD synergistically improved colitis mice.This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice.The experimental colitis model was established by administering 3%dextran sulphate sodium(DSS)to mice for 7 days,followed by CP,AZ and CPAZ treatment for an additional 7 days.M1/M2 macrophage polarization levels,glucose metabolites levels and pyruvate dehydrogenase kinase 4(PDK4)expression were analyzed using flow cytometry,Western blot,immunofluorescence and targeted glucose metabolomics.The findings indicated that CP inhibited M1 macrophage polarization,decreased inflammatory metabolites associated with tricarboxylic acid(TCA)cycle,and suppressed PDK4 expression and pyruvate dehydrogenase(PDH)(Ser-293)phosphorylation level.AZ enhanced M2 macrophage polarization,increased lactate axis metabolite lactate levels,and upregulated PDK4 expression and PDH(Ser-293)phosphorylation level.TCA cycle blocker AG-221 and adeno-associated virus(AAV)-PDK4 partially negated CP’s inhibition of M1 macrophage polarization.Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate(DCA)partially reduced AZ’s activation of M2 macrophage polarization.In conclusion,the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming.Specifically,CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition,while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.展开更多
Pain is a signal of inflammation that can have both protective and pathogenic effects.Macrophages,significant components of the immune system,play crucial roles in the occurrence and development of pain,particularly i...Pain is a signal of inflammation that can have both protective and pathogenic effects.Macrophages,significant components of the immune system,play crucial roles in the occurrence and development of pain,particularly in neuroimmune communication.Macrophages exhibit plasticity and heterogeneity,adopting either pro-inflammatory M1 or anti-inflammatory M2 phenotypes depending on their functional orientation.Recent research highlights the contribution of macrophages to pain dynamics by undergoing changes in their functional polarity,leading to macrophage activation,tissue infiltration,and cytokine secretion.M1 macrophages release pro-inflammatory mediators that are not only essential in defending against infections,but also contributing to tissue damage and the elicitation of pain.However,this process can be counteracted by M2 macrophages,facilitating pain relief through producing anti-inflammatory cytokines and opioid peptides or enhancing efferocytosis.M1 and M2 macrophages play important roles in both the initiation and mitigation of pain.展开更多
巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋...巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。展开更多
目的:观察淫羊藿苷(ICA)对脂蛋白多糖诱导的巨噬细胞RAW264.7细胞M1/M2炎症表型转化作用。方法:采用M1/M2经典刺激方法后,Real-time PCR法检测M1型巨噬细胞标志基因IL-6、TNF-α和M2型巨噬细胞标志基因IL-10、Arg等的m RNA表达情况。并...目的:观察淫羊藿苷(ICA)对脂蛋白多糖诱导的巨噬细胞RAW264.7细胞M1/M2炎症表型转化作用。方法:采用M1/M2经典刺激方法后,Real-time PCR法检测M1型巨噬细胞标志基因IL-6、TNF-α和M2型巨噬细胞标志基因IL-10、Arg等的m RNA表达情况。并观察ICA不同浓度(50μg/m L、100μg/m L)以及以不同时间(6h、12h、24h)分别干预巨噬细胞M1及M2相关基因的表达变化情况。在将巨噬细胞诱导M1型后,通过Real-time PCR法检测ICA在最适浓度和最适时间干预下,M1及M2标志基因表达变化,并分析ICA对M1型巨噬细胞向M2亚型转化的诱导作用。结果:M1/M2经典方法刺激后,M1型巨噬细胞标志分子IL-6、TNF-αm RNA与M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05)。且ICA浓度为100μg/m L时,M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05),诱导巨噬细胞向M2方向分化。100μg/m L ICA干预12h后,对M1/M2不同标志分子m RNA表达变化产生明显影响(P<0.05)。100μg/m L ICA作用于LPS+IFN-γ诱导的M1巨噬细胞后,M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05),M1型巨噬细胞标志分子IL-6 m RNA表达下降(P<0.05)。结论:ICA可以诱导体外培养巨噬细胞RAW264.7向抗炎亚型M型方向分化,并可以诱导已经分化的促炎亚型M1巨噬细胞向抗炎亚型M2方向转化。展开更多
基金supported by the National Natural Science Foundation of China(Nos.82374325 and 82074322)GDAS'ProjectofScience and Technology Development(No.2022GDASZH-2022010110).
文摘Ulcerative colitis(UC)is a chronic and non-specific inflammatory bowel disease(IBD).Huanglian Ganjiang decoction(HGD),derived from ancient book Beiji Qianjin Yao Fang,has demonstrated efficacy in treating UC patients traditionally.Previous research established that the compatibility of cold herb Coptidis Rhizoma+Phellodendri Chinensis Cortex(CP)and hot herb Angelicae Sinensis Radix+Zingiberis Rhizoma(AZ)in HGD synergistically improved colitis mice.This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice.The experimental colitis model was established by administering 3%dextran sulphate sodium(DSS)to mice for 7 days,followed by CP,AZ and CPAZ treatment for an additional 7 days.M1/M2 macrophage polarization levels,glucose metabolites levels and pyruvate dehydrogenase kinase 4(PDK4)expression were analyzed using flow cytometry,Western blot,immunofluorescence and targeted glucose metabolomics.The findings indicated that CP inhibited M1 macrophage polarization,decreased inflammatory metabolites associated with tricarboxylic acid(TCA)cycle,and suppressed PDK4 expression and pyruvate dehydrogenase(PDH)(Ser-293)phosphorylation level.AZ enhanced M2 macrophage polarization,increased lactate axis metabolite lactate levels,and upregulated PDK4 expression and PDH(Ser-293)phosphorylation level.TCA cycle blocker AG-221 and adeno-associated virus(AAV)-PDK4 partially negated CP’s inhibition of M1 macrophage polarization.Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate(DCA)partially reduced AZ’s activation of M2 macrophage polarization.In conclusion,the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming.Specifically,CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition,while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
基金supported by the Natural Science Foundation of Hunan Province(2021JJ41060,2022JJ30972)the Changsha Municipal Natural Science Foundation(kq2014280)+1 种基金the Research Program Project of Hunan Health Commission(B202304119634)China。
文摘Pain is a signal of inflammation that can have both protective and pathogenic effects.Macrophages,significant components of the immune system,play crucial roles in the occurrence and development of pain,particularly in neuroimmune communication.Macrophages exhibit plasticity and heterogeneity,adopting either pro-inflammatory M1 or anti-inflammatory M2 phenotypes depending on their functional orientation.Recent research highlights the contribution of macrophages to pain dynamics by undergoing changes in their functional polarity,leading to macrophage activation,tissue infiltration,and cytokine secretion.M1 macrophages release pro-inflammatory mediators that are not only essential in defending against infections,but also contributing to tissue damage and the elicitation of pain.However,this process can be counteracted by M2 macrophages,facilitating pain relief through producing anti-inflammatory cytokines and opioid peptides or enhancing efferocytosis.M1 and M2 macrophages play important roles in both the initiation and mitigation of pain.
文摘巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。
文摘目的:观察淫羊藿苷(ICA)对脂蛋白多糖诱导的巨噬细胞RAW264.7细胞M1/M2炎症表型转化作用。方法:采用M1/M2经典刺激方法后,Real-time PCR法检测M1型巨噬细胞标志基因IL-6、TNF-α和M2型巨噬细胞标志基因IL-10、Arg等的m RNA表达情况。并观察ICA不同浓度(50μg/m L、100μg/m L)以及以不同时间(6h、12h、24h)分别干预巨噬细胞M1及M2相关基因的表达变化情况。在将巨噬细胞诱导M1型后,通过Real-time PCR法检测ICA在最适浓度和最适时间干预下,M1及M2标志基因表达变化,并分析ICA对M1型巨噬细胞向M2亚型转化的诱导作用。结果:M1/M2经典方法刺激后,M1型巨噬细胞标志分子IL-6、TNF-αm RNA与M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05)。且ICA浓度为100μg/m L时,M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05),诱导巨噬细胞向M2方向分化。100μg/m L ICA干预12h后,对M1/M2不同标志分子m RNA表达变化产生明显影响(P<0.05)。100μg/m L ICA作用于LPS+IFN-γ诱导的M1巨噬细胞后,M2型巨噬细胞标志分子IL-10、Arg m RNA表达明显升高(P<0.05),M1型巨噬细胞标志分子IL-6 m RNA表达下降(P<0.05)。结论:ICA可以诱导体外培养巨噬细胞RAW264.7向抗炎亚型M型方向分化,并可以诱导已经分化的促炎亚型M1巨噬细胞向抗炎亚型M2方向转化。
