Exploring the Role of Secondary Metabolites from Plants and Microbes as Modulators of Macrophage Differentiation.

Prakhar Sharma, Modi Kiran Piyushbhai, Kaliyamurthi Venkatachalam, Ambika Binesh
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Abstract

Recent research has uncovered that secondary metabolites-biologically active compounds produced by plants, microbes, and other organisms-play a significant role in regulating the differentiation and function of macrophages. Macrophages, key components of the innate immune system, are crucial for a wide range of physiological processes, including immune response modulation, tissue homeostasis, and host defense against pathogens. This research delves into the mechanisms by which secondary metabolites influence macrophage differentiation signaling pathways, with a focus on how specific compounds affect macrophage polarization and functional phenotypes. Understanding these effects can open new avenues for developing therapeutic strategies that target macrophage-mediated immune responses. Secondary metabolites, such as nitrogen (N) and sulfur (S) containing compounds, terpenoids, and phenolic compounds from plants and microbes, can modulate macrophage differentiation by influencing cytokine production and activity. The activation of signaling pathways in macrophages involves multiple receptors and transcription factors, including IFN-γ receptor activation leading to STAT1 activation, TLR4 triggering IRF5, NFκB, and AP1, IL-4 receptor activation leading to STAT6 and IRF4 activation, PPARγ activation via the fatty acid receptor, TLR4 increasing CREB and C/EBP levels. The complex interplay between transcription factors and cytokines is crucial for maintaining the balance between the M1 and M2 states of macrophages. Despite these insights, further research is needed to unravel the specific molecular mechanisms involved and to identify promising secondary metabolites that could be translated into clinical applications.

探索植物和微生物次生代谢物作为巨噬细胞分化调节剂的作用
最近的研究发现,次生代谢物--由植物、微生物和其他生物产生的生物活性化合物--在调节巨噬细胞的分化和功能方面发挥着重要作用。巨噬细胞是先天性免疫系统的关键组成部分,对免疫反应调节、组织稳态和宿主抵御病原体等一系列生理过程至关重要。本研究深入探讨次生代谢物影响巨噬细胞分化信号通路的机制,重点研究特定化合物如何影响巨噬细胞的极化和功能表型。了解这些影响可为开发针对巨噬细胞介导的免疫反应的治疗策略开辟新途径。次生代谢物,如植物和微生物中的含氮(N)和含硫(S)化合物、萜类化合物和酚类化合物,可通过影响细胞因子的产生和活性来调节巨噬细胞的分化。巨噬细胞信号通路的激活涉及多种受体和转录因子,包括 IFN-γ 受体激活导致 STAT1 激活,TLR4 触发 IRF5、NFκB 和 AP1,IL-4 受体激活导致 STAT6 和 IRF4 激活,PPARγ 通过脂肪酸受体激活,TLR4 提高 CREB 和 C/EBP 水平。转录因子和细胞因子之间复杂的相互作用对于维持巨噬细胞 M1 和 M2 状态之间的平衡至关重要。尽管有了这些见解,但仍需进一步研究,以揭示其中涉及的具体分子机制,并确定有希望转化为临床应用的次生代谢物。
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