Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Zhou, Haicun; Yan, Xin-Yan; Yu, Wenwen; Liang, Xiaoqin; Du, Xiaoyan; Liu, Zhichang; Long, Jian-Ping; Zhao, Guanghui; Liu, Hongbin

doi:10.1080/08830185.2021.1955876

Cited by 89 publications

(60 citation statements)

References 130 publications

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“…Lactic acid is a regulator of macrophage metabolism and can prevent excessive inflammation. Studies have revealed a new connection between lactic acid and the control of uterine inflammation, and found that high levels of lactic acid act on uterine GPR81 and downregulate pro-inflammatory genes (Zhou et al, 2021). Taurine is an endogenous anti-injury substance in humans.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

Liu

Wang

et al. 2021

Front. Pharmacol.

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Dysmenorrhea refers to a kind of uterine cramping pain that occurs in women during the period of menstrual. Guizhi Fuling Capsules are mainly used for the treatment of various pain syndromes and especially effective in treating primary dysmenorrhea. However, the research on its modern pharmacology and mechanism of action have not been thoroughly carried out. It is not clear about the main active ingredients, potential targets and metabolic pathways involved in its efficacy. Therefore, this research project employed estradiol benzoate sensitization combined with oxytocin pain to construct the cold coagulation syndrome dysmenorrhea model, observed the anti-dysmenorrhea effect of Guizhi Fuling Capsules, and used the metabolomics to explore its mechanism. The results showed that Guizhi Fuling Capsules could considerably reduce the number of writhing times in dysmenorrhea rats, increasing the level of PGE2 and β-EP and reducing the contents of PGF2α in rat serum. Pathological sections of uterus and ovaries also showed that Guizhi Fuling Capsules could significantly relieve endometrial hyperplasia and improve ovarian function. The LC/MS-based metabolomics of rat uterine indicated that the model group has a great deviation from the control group. Compared with the model group, the Guizhi Fuling Capsules group had a tendency to shift to the control group, and the main metabolic changes was mainly concentrated on saturated and unsaturated fatty acids. Among them, arachidonic acid is in a pivotal position, and the expression of its rate-limiting enzyme (COX-2) involved in its cyclooxygenase metabolic pathway was significantly up-regulated in the model group, but significantly decreased after the intervention of Guizhi Fuling Capsules. In conclusion, Guizhi Fuling Capsules can effectively relieve primary dysmenorrhea, and this effect may be attributed to the regulation effects of Guizhi Fuling Capsules on endogenous metabolism, such as inhibiting arachidonic acid converted to prostaglandins through downregulate the expression of COX-2, which plays an anti-inflammatory effect.

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Section: Discussionmentioning

confidence: 99%

Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

Liu

Wang

et al. 2021

Front. Pharmacol.

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“…Besides, secretion of TNF-a by macrophages is inhibited by acidic pH (112). Additionally, long term effect of exogenous lactate in M1 macrophages, trigger an endogenous 'lactate clock' that induce an M2 phenotype by metabolic reprograming through the epigenetic mechanism by lactylation and acetylation of histone H3 (113,114). This effect could to assist with repairing collateral damage produced by the host during infection and to explain the anti-inflammatory effects of lactate after 24 h (85,115,116).…”

Section: Lactate Activity In Macrophages and Mast Cellsmentioning

confidence: 99%

Role of Lactate in Inflammatory Processes: Friend or Foe

et al. 2022

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During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.

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“…Studies show lactate enhances the production of MDSC from the bone marrow of mice while suppressing NK cells leading to weakened cytotoxicity [ 201 ] ( Figure 1 C). Furthermore, lactate skews macrophages toward the tumor-promoting M2 phenotype and upregulates PD-L1 to enhance immune escape [ 202 , 203 , 204 ]. Therefore, an increased lactate concentration in the TME serves as not only a potential therapeutic target, but also a poor prognosticator [ 198 ].…”

Section: Tumor Stroma Mediators Chemical Components and Physical Factors Constitute The Tumor Microenvironment (Tme)mentioning

confidence: 99%

Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity

Lin

Liu

Lofland

et al. 2022

Cancers

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Breast cancer is the most common malignancy among females in western countries, where women have an overall lifetime risk of >10% for developing invasive breast carcinomas. It is not a single disease but is composed of distinct subtypes associated with different clinical outcomes and is highly heterogeneous in both the molecular and clinical aspects. Although tumor initiation is largely driven by acquired genetic alterations, recent data suggest microenvironment-mediated immune evasion may play an important role in neoplastic progression. Beyond surgical resection, radiation, and chemotherapy, additional therapeutic options include hormonal deactivation, targeted-signaling pathway treatment, DNA repair inhibition, and aberrant epigenetic reversion. Yet, the fatality rate of metastatic breast cancer remains unacceptably high, largely due to treatment resistance and metastases to brain, lung, or bone marrow where tumor bed penetration of therapeutic agents is limited. Recent studies indicate the development of immune-oncological therapy could potentially eradicate this devastating malignancy. Evidence suggests tumors express immunogenic neoantigens but the immunity towards these antigens is frequently muted. Established tumors exhibit immunological tolerance. This tolerance reflects a process of immune suppression elicited by the tumor, and it represents a critical obstacle towards successful antitumor immunotherapy. In general, immune evasive mechanisms adapted by breast cancer encompasses down-regulation of antigen presentations or recognition, lack of immune effector cells, obstruction of anti-tumor immune cell maturation, accumulation of immunosuppressive cells, production of inhibitory cytokines, chemokines or ligands/receptors, and up-regulation of immune checkpoint modulators. Together with altered metabolism and hypoxic conditions, they constitute a permissive tumor microenvironment. This article intends to discern representative incidents and to provide potential innovative therapeutic regimens to reinstate tumoricidal immunity.

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Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Cited by 89 publications

References 130 publications

Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

Role of Lactate in Inflammatory Processes: Friend or Foe

Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity

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