Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy

Pan, Xiaohua; Zhu, Qing; Dong, Xiaoliang; Li, Jiahong; Li, He; Ren, Zhengran; Li, Binbin; Pan, Li-Long; Sun, Jia

doi:10.1016/j.pharmthera.2022.108176

Cited by 88 publications

(51 citation statements)

References 176 publications

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“…The LPS-induced metabolic switch from OXPHOS to aerobic glycolysis in macrophages is associated with HIF1α activation (42). This metabolic pattern switch depends on the stabilization of HIF-1α and resulting in in the expression of key glycolytic proteins, such as GLUT1, PKM2, and PFKFB3 (43). Here, our results showed that LPS significantly promoted the expression of HIF-1α, which was ameliorated by CTS treatment (Figure 6E).…”

Section: Cts Regulates Raw2647 Macrophage Metabolism By Activating Am...mentioning

confidence: 51%

Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage

Wang

Guo

et al. 2023

Front. Med.

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BackgroundAcute lung injury (ALI) is a life-threatening inflammatory disease without effective therapeutic regimen. Macrophage polarization plays a key role in the initiation and resolution of pulmonary inflammation. Therefore, modulating macrophage phenotype is a potentially effective way for acute lung injury. Cryptotanshinone (CTS) is a lipophilic bioactive compound extracted from the root of Salvia miltiorrhiza with a variety of pharmacological effects, especially the anti-inflammatory role. In this study, we investigated the therapeutic and immunomodulatory effects of CTS on ALI.Materials and methodsThe rat model of ALI was established by intratracheal instillation of LPS (5 mg/kg) to evaluate the lung protective effect of CTS in vivo and to explore the regulation of CTS on the phenotype of lung macrophage polarization. LPS (1 μg/mL) was used to stimulate RAW264.7 macrophages in vitro to further explore the effect of CTS on the polarization and metabolic reprogramming of RAW264.7 macrophages and to clarify the potential mechanism of CTS anti-ALI.ResultsCTS significantly improved lung function, reduced pulmonary edema, effectively inhibited pulmonary inflammatory infiltration, and alleviated ALI. Both in vivo and in vitro results revealed that CTS inhibited the differentiation of macrophage into the M1 phenotype and promoted polarization into M2 phenotype during ALI. Further in vitro studies indicated that CTS significantly suppressed LPS-induced metabolic transition from aerobic oxidation to glycolysis in macrophages. Mechanistically, CTS blocked LPS-induced metabolic transformation of macrophages by activating AMPK.ConclusionThese findings demonstrated that CTS regulates macrophage metabolism by activating AMPK, and then induced M1-type macrophages to transform into M2-type macrophages, thereby alleviating the inflammatory response of ALI, suggesting that CTS might be a potential anti-ALI agent.

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Section: Cts Regulates Raw2647 Macrophage Metabolism By Activating Am...mentioning

confidence: 51%

Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage

Wang

Guo

et al. 2023

Front. Med.

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“…It is well known that immune homeostasis depends on immune cells and immune molecules. Innate immune cells such as M1 macrophages, NK cells, immunogenic DC cells, and adaptive immune cells such as CD4+ and CD8+ cells play a role in promoting mucosal immune and inflammatory responses in UC [ 29 – 31 ]; While M2 macrophages, regulatory NK cells, regulatory DC cells in innate immune cells, and Tregs cells in adaptive immune cells can release a variety of anti-inflammatory factors to play an antagonistic role in reducing intestinal damage in UC [ 32 – 34 ]. After immune cell correlation analysis of novel marker genes, we found that SLC6A14 , TIMP1 , and IRAK3 , whose expression were up-regulated in UC, also increased the pro-immune and pro-inflammatory cells they affected; While the down-regulated expression of HMGCS2 and ABOPEC3B also reduced the proportion of immune cells with the anti-immune response and anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Screening of ulcerative colitis biomarkers and potential pathways based on weighted gene co-expression network, machine learning and ceRNA hypothesis

et al. 2022

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Background Ulcerative colitis (UC) refers to an intractable intestinal inflammatory disease. Its increasing incidence rate imposes a huge burden on patients and society. The UC etiology has not been determined, so screening potential biomarkers is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. Methods The microarray datasets of intestinal mucosal biopsy of UC patients were selected from the GEO database, and integrated with R language to screen differentially expressed genes and draw proteins interaction network diagrams. GO, KEGG, DO and GSEA enrichment analyses were performed to explore their biological functions. Through machine learning and WGCNA analysis, targets that can be used as UC potential biomarkers are screened out. ROC curves were drawn to verify the reliability of the results and predicted the mechanism of marker genes from the aspects of immune cell infiltration, co-expression analysis, and competitive endogenous network (ceRNA). Results Two datasets GSE75214 and GSE87466 were integrated for screening, and a total of 107 differentially expressed genes were obtained. They were mainly related to biological functions such as humoral immune response and inflammatory response. Further screened out five marker genes, and found that they were associated with M0 macrophages, quiescent mast cells, M2 macrophages, and activated NK cells in terms of immune cell infiltration. The co-expression network found significant co-expression relationships between 54 miRNAs and 5 marker genes. According to the ceRNA hypothesis, NEAT1-miR-342-3p/miR-650-SLC6A14, NEAT1-miR-650-IRAK3, and XIST-miR-342-3p-IRAK3 axes were found as potential regulatory pathways in UC. Conclusion This study screened out five biomarkers that can be used for the diagnosis and treatment of UC, namely SLC6A14, TIMP1, IRAK3, HMGCS2, and APOBEC3B. Confirmed that they play a role in the occurrence and development of UC at the level of immune infiltration, and proposed a potential RNA regulatory pathway that controls the progression of UC.

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“…Although pathogenic microorganisms can directly destroy host periodontal tissues by releasing virulence factors and metabolites, the host immune response plays an equally important role in the progression of periodontitis (Bosshardt, 2017;Bunte and Beikler, 2019;Pan et al, 2019). The host immune response to microorganisms can be divided into intrinsic immune responses and adaptive immune responses.…”

Section: Immune Mechanism Associations Of Periodontitis and Ibdmentioning

confidence: 99%

“…Neutrophils and macrophages play an important role in the intrinsic immune response in IBD. Neutrophil activation is followed by the disruption of the intestinal epithelial barrier through the production of high levels of reactive oxygen species (ROS) and the release of proteases, pro-inflammatory cytokines and chemokines, such as IL-8, TNF-a and leukotriene B4 (LTB4) (Weŕa et al, 2016;Zhou and Liu, 2017;Kvedaraite, 2021); the number of macrophages in the intestinal mucosa in IBD patients is increased, and the intestinal epithelium damage is aggravated by producing a large number of proinflammatory and chemokines, such as TNF-a, IL-1b, IL-12 and IL-23, and enhancing the Th1 and Th17 cell responses (Bain and Schridde, 2018;Na et al, 2019;Pan et al, 2022). CD4 + T cell-mediated adaptive immunity also plays a crucial role in the development of IBD, and Neurath et al found that CD is characterized by Th1 immune responses, with Th1 increasing the secretion of the pro-inflammatory factors IFN-g and IL-2, while UC is a Th2-mediated disease that produces excessive amounts of IL-5 and IL-13 (Neurath et al, 2002).…”

Section: Immune Mechanism Associations Of Periodontitis and Ibdmentioning

confidence: 99%

The effect of the “Oral-Gut” axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations

Zhou

Wang

et al. 2023

Front. Cell. Infect. Microbiol.

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Periodontitis and inflammatory bowel diseases (IBD) are inflammatory diseases of the gastrointestinal tract that share common features of microbial-induced ecological dysregulation and host immune inflammatory response. The close relationship between periodontitis and IBD is characterized by a higher prevalence of IBD in patients with periodontitis and a higher prevalence and severity of periodontitis in patients with IBD, indicating that periodontitis and IBD are different from the traditional independent diseases and form an “Oral-Gut” axis between the two, which affect each other and thus form a vicious circle. However, the specific mechanisms leading to the association between the two are not fully understood. In this article, we describe the interconnection between periodontitis and IBD in terms of microbial pathogenesis and immune dysregulation, including the ectopic colonization of the gut by pathogenic bacteria associated with periodontitis that promotes inflammation in the gut by activating the host immune response, and the alteration of the oral microbiota due to IBD that affects the periodontal inflammatory response. Among the microbial factors, pathogenic bacteria such as Klebsiella, Porphyromonas gingivalis and Fusobacterium nucleatum may act as the microbial bridge between periodontitis and IBD, while among the immune mechanisms, Th17 cell responses and the secreted pro-inflammatory factors IL-1β, IL-6 and TNF-α play a key role in the development of both diseases. This suggests that in future studies, we can look for targets in the “Oral-Gut” axis to control and intervene in periodontal inflammation by regulating periodontal or intestinal flora through immunological methods.

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Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy

Cited by 88 publications

References 176 publications

Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage

Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage

Screening of ulcerative colitis biomarkers and potential pathways based on weighted gene co-expression network, machine learning and ceRNA hypothesis

The effect of the “Oral-Gut” axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations

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