E3 ubiquitin ligase TRIM31: A potential therapeutic target.

Ubiquitination is a key mechanism for post-translational protein modification, affecting protein localization, metabolism, degradation and various cellular physiological processes. Dysregulation of ubiquitination is associated with the pathogenesis of various diseases, such as tumors and cardiovascular diseases, making it a primary area of interest in biochemical research and drug development endeavors. E3 ubiquitin ligases play a pivotal role in modulating the ubiquitination of substrate proteins through their unique recognition functions. TRIM31, a member of the TRIM family of E3 ubiquitin ligases, is aberrantly expressed in different pathophysiological conditions. The biological function of TRIM31 is associated with the occurrence and development of diverse diseases. TRIM31 has been demonstrated to inhibit inflammation by promoting ubiquitin-proteasome-mediated degradation of the sensing protein NLRP3 in the inflammasome. TRIM31 mediates ubiquitination of MAVS, inducing the formation of prion-like aggregates, and triggering innate antiviral immune responses. TRIM31 is also implicated in tumor pathophysiology through its ability to promote ubiquitination of the tumor suppressor protein p53. These findings indicate that TRIM31 is a potential therapeutic target, and subsequent in-depth research of TRIM31 is anticipated to provide information on its clinical application in therapy.

Unique method for removal of knotted lumbar epidural catheter: A case report.

BACKGROUND: Combined spinal-epidural (CSE) anesthesia is the preferred anesthesia method for cesarean delivery. The use of an epidural catheter is essential for administering additional drugs intraoperatively and managing postoperative pain. However, the insertion of epidural catheters is associated with various complications, such as total spinal anesthesia, symptoms indicative of spinal nerve root irritation, and challenges in epidural catheter removal. CASE SUMMARY: We present a case report of a challenging epidural catheter removal due to knotting. The lumbar computed tomography scan results revealed that the catheter formed a tight knot in the epidural space. We used a novel extubation method and successfully removed the catheter. CONCLUSION: The operator can use opposite forces to "spiral" apart the spinal joints by positioning the patient's body in a specific position. The findings indicate that, when combined with imaging examination results, this method is effective for the removal of epidural catheters.

P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.

Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

LncRNA-mediated Modulation of Endothelial Cells: Novel Progress in the Pathogenesis of Coronary Atherosclerotic Disease.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

TRIM65 Suppresses oxLDL-induced Endothelial Inflammation by Interaction with VCAM-1 in Atherogenesis.

BACKGROUND AND OBJECTIVE: Endothelial cell activation, characterized by increased levels of vascular cell adhesion molecule 1 (VCAM-1), plays a crucial role in the development of atherosclerosis (AS). Therefore, inhibition of VCAM-1-mediated inflammatory response is of great significance in the prevention and treatment of AS. The tripartite motif (TRIM) protein-TRIM65 is involved in the regulation of cancer development, antivirals and inflammation. We aimed to study the functions of TRIM65 in regulating endothelial inflammation by interacting with VCAM-1 in atherogenesis. METHODS AND RESULTS: In vitro, we report that human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (oxLDL) significantly upregulate the expression of TRIM65 in a time- and dose-dependent manner. Overexpression of TRIM65 reduces oxLDL-triggered VCAM-1 protein expression, decreases monocyte adhesion to HUVECs and inhibits the production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α as well as endothelial oxLDL transcytosis. In contrast, siRNA-mediated knockdown of TRIM65 promotes the expression of VCAM-1, resulting in increased adhesion of monocytes and the release of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α and enhances endothelial oxLDL transcytosis. In vivo, we measured the high expression of TRIM65 in ApoE-/- mouse aortic plaques compared to C57BL/6J mouse aortic plaques. Then, we examined whether the blood levels of VCAM-1 were higher in TRIM65 knockout ApoE-/- mice than in control mice induced by a Western diet. Furthermore, Western blot results showed that the protein expression of VCAM-1 was markedly enhanced in TRIM65 knockout ApoE-/- mouse aortic tissues compared to that of the controls. Immunofluorescence staining revealed that the expression of VCAM-1 was significantly increased in atherosclerotic plaques of TRIM65-/-/ApoE-/- aortic vessels compared to ApoE-/- controls. Mechanistically, TRIM65 specifically interacts with VCAM-1 and targets it for K48-linked ubiquitination. CONCLUSION: Our studies indicate that TRIM65 attenuates the endothelial inflammatory response by targeting VCAM-1 for ubiquitination and provides a potential therapeutic target for the inhibition of endothelial inflammation in AS.

The role of ROS-induced pyroptosis in CVD.

Cardiovascular disease (CVD) is the number one cause of death in the world and seriously threatens human health. Pyroptosis is a new type of cell death discovered in recent years. Several studies have revealed that ROS-induced pyroptosis plays a key role in CVD. However, the signaling pathway ROS-induced pyroptosis has yet to be fully understood. This article reviews the specific mechanism of ROS-mediated pyroptosis in vascular endothelial cells, macrophages, and cardiomyocytes. Current evidence shows that ROS-mediated pyroptosis is a new target for the prevention and treatment of cardiovascular diseases such as atherosclerosis (AS), myocardial ischemia-reperfusion injury (MIRI), and heart failure (HF).

Understanding the Potential Function of Perivascular Adipose Tissue in Abdominal Aortic Aneurysms: Current Research Status and Future Expectation.

An abdominal aortic aneurysm (AAA) is a progressive dilatation of the vascular wall occurring below the aortic fissure, preferably occurring below the renal artery. The molecular mechanism of AAA has not yet been elucidated. In the past few decades, research on abdominal aortic aneurysm has been mainly focused on the vessel wall, and it is generally accepted that inflammation and middle layer fracture of the vessel wall is the core steps in the development of AAA. However, perivascular adipose tissue plays a non-negligible role in the occurrence and development of AAA. The position of PVAT plays a supporting and protective role on the vascular wall, but the particularity of the location makes it not only have the physiological function of visceral fat; but also can regulate the vascular function by secreting a large number of adipokines and cytokines. An abdominal aortic aneurysm is getting higher and higher, with a vascular rupture, low rescue success rate, and extremely high lethality rate. At present, there is no drug to control the progression or reverse abdominal aortic aneurysm. Therefore, it is critical to deeply explore the mechanism of abdominal aortic aneurysms and find new therapeutic ways to inhibit abdominal aortic aneurysm formation and disease progression. An abdominal aortic aneurysm is mainly characterized by inflammation of the vessel wall and matrix metalloprotein degradation. In this review, we mainly focus on the cytokines released by the perivascular adipose tissue, summarize the mechanisms involved in the regulation of abdominal aortic aneurysms, and provide new research directions for studying abdominal aortic aneurysms.

Outlook of Ferroptosis-Targeted Lipid Peroxidation in Cardiovascular Disease.

Lipid metabolism is a complex biochemical process that regulates normal cell activity and death. Ferroptosis is a novel mode of programmed cell death different from apoptosis, pyroptosis, and autophagy. Abnormal lipid metabolism may lead to lipid peroxidation and cell rupture death, which are regulated by lipoxygenase (LOX), long-chain acyl-coA synthases, and antioxidant enzymes. Alternatively, Fe2+ and Fe3+ are required for the activity of LOXs and ferroptosis, and Fe2+ can significantly accelerate lipid peroxidation in ferroptosis. Abnormal lipid metabolism is a certain risk factor for cardiovascular disease. In recent years, the important role of ferroptosis in developing cardiovascular disease has been increasingly reported. Reducing lipid accumulation could reduce the occurrence of ferroptosis, thus alleviating cardiovascular disease deterioration. This article reviews the relationship of lipid peroxidation to the general mechanism of ferroptosis and highlights lipid peroxidation as the common point of ferroptosis and cardiovascular disease.

Development of hydrogen sulfide donors for anti-atherosclerosis therapeutics research: Challenges and future priorities.

Hydrogen sulfide (H2S), a gas transmitter found in eukaryotic organisms, plays an essential role in several physiological processes. H2S is one of the three primary biological gas transmission signaling mediators, along with nitric oxide and carbon monoxide. Several animal and in vitro experiments have indicated that H2S can prevent coronary endothelial mesenchymal transition, reduce the expression of endothelial cell adhesion molecules, and stabilize intravascular plaques, suggesting its potential role in the treatment of atherosclerosis (AS). H2S donors are compounds that can release H2S under certain circumstances. Development of highly targeted H2S donors is a key imperative as these can allow for in-depth evaluation of the anti-atherosclerotic effects of exogenous H2S. More importantly, identification of an optimal H2S donor is critical for the creation of H2S anti-atherosclerotic prodrugs. In this review, we discuss a wide range of H2S donors with anti-AS potential along with their respective transport pathways and design-related limitations. We also discuss the utilization of nano-synthetic technologies to manufacture H2S donors. This innovative and effective design example sheds new light on the production of highly targeted H2S donors.

Alpha-Momorcharin Inhibits Proinflammatory Cytokine Expression by M1 Macrophages but Not Anti-Inflammatory Cytokine Expression by M2 Macrophages.

Background: Alpha-momorcharin (α-MMC) is a natural medicine derived from bitter melon and has been found to exert immunomodulatory effects. Our previous study indicated that α-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines. Methods: LPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after α-MMC was administered. Then, a LPS-induced acute pneumonia mouse model was established, the proinflammatory cytokines levels and inflammatory lesions in lung tissues were examined by ELISA or H&E staining. Furthermore, omics screening analysis and Western blotting verification were performed on TLR4 and JAK1-STAT6 signalling pathway-related proteins to elucidate the regulatory mechanism of α-MMC in those M1 macrophages and M2 macrophages. Results: At a noncytotoxic dose of 0.3 µg/mL, α-MMC significantly inhibited the LPS-induced expression of inflammatory cytokines, such as TNF-α, IL-1ß, IL-6, IL-8, MIP-1α and MCP-1, by M1 macrophages in a time-dependent manner, but α-MMC did not inhibit the IL-4-induced synthesis of anti-inflammatory cytokines, such as IL-10, IL-1RA, EGF, VEGF, TGF-ß and CCL22, by M2 macrophages. Moreover, α-MMC also inhibited inflammatory cytokine expression in an LPS-induced acute pneumonia mouse model and alleviated inflammation in lung tissues. Furthermore, omics screening and Western blotting analysis confirmed that α-MMC inhibited TAK1/p-TAK1 and subsequently blocked the downstream MAPK and NF-κB pathways, thus inhibiting the LPS-induced inflammatory cytokine expression. Conclusion: Our results reveal that α-MMC inhibits proinflammatory cytokine expression by M1 macrophages but not anti-inflammatory cytokine expression by M2 macrophages. The efficacy of α-MMC in selectively inhibiting proinflammatory cytokine expression renders it particularly suitable for the treatment of severe inflammation and autoimmune diseases characterized by cytokine storms.

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck in Southeast Asia and southern China. The Phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in processes related to tumour initiation/progression, such as proliferation, apoptosis, metastasis, and drug resistance, and is closely related to the clinicopathological features of NPC. In addition, key genes involved in the PI3K/AKT/mTOR signalling pathway undergo many changes in NPC. More interestingly, a growing body of evidence suggests an interaction between this signalling pathway and microRNAs (miRNAs), a class of small noncoding RNAs. Therefore, in this review, we discuss the interactions between key components of the PI3K/AKT/mTOR signalling pathway and various miRNAs and their importance in NPC pathology and explore potential diagnostic biomarkers and therapeutic targets.

The role of adipose tissue-derived hydrogen sulfide in inhibiting atherosclerosis.

Hydrogen sulfide (H2S) is the third gaseous signaling molecule discovered in the body after NO and CO and plays an important organismal protective role in various diseases. Within adipose tissue, related catalytic enzymes (cystathionine-ß-synthetase, cystathionine-γ-lyase, and 3-mercaptopyruvate transsulfuration enzyme) can produce and release endogenous H2S. Atherosclerosis (As) is a pathological change in arterial vessels that is closely related to abnormal glucose and lipid metabolism and a chronic inflammatory response. Previous studies have shown that H2S can act on the cardiovascular system, exerting effects such as improving disorders of glycolipid metabolism, alleviating insulin resistance, protecting the function of vascular endothelial cells, inhibiting vascular smooth muscle cell proliferation and migration, regulating vascular tone, inhibiting the inflammatory response, and antagonizing the occurrence and development of As.

TRIMs: Generalists Regulating the NLRP3 Inflammasome Signaling Pathway.

Inflammation is a double-edged sword. The moderate inflammatory response is a fundamental defense mechanism produced by the body's resistance to dangerous stimuli and a repair process of the body itself. Increasing studies have confirmed that the overactivation of the inflammasome is involved in the occurrence and development of inflammatory diseases. Strictly controlling the overactivation of the inflammasome and preventing excessive inflammatory response have always been the research focus on inflammatory diseases. However, the endogenous regulatory mechanism of inflammasome is not completely clear. The tripartite motif (TRIM) protein is one of the members of E3 ligases in the process of ubiquitination. The universality and importance of the functions of TRIM members are recognized, including the regulation of inflammatory response. This article will focus on research on the relationship between TRIMs and NLRP3 Inflammasome, which may help us make some references for future related research and the discovery of treatment methods.

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

Cross-link between ferroptosis and nasopharyngeal carcinoma: New approach to radiotherapy sensitization.

Ferroptosis is a recently discovered special type of regulated cell death that is strongly associated with both homeostasis maintenance and cancer development. Previous studies have indicated that a number of small-molecular agents inducing ferroptosis have great potential in the treatment of different types of cancer, including breast, pancreatic, prostate and head and neck cancer. However, the role of ferroptosis in nasopharyngeal carcinoma (NPC) has remained to be fully determined. To the best of our knowledge, no review of the currently available studies on this subject has been published to date. The metabolism and expression of specific genes that regulate ferroptosis may represent a promising radiosensitization target in cancer treatment. The aim of the present review was to describe the cross-link between ferroptosis and NPC and to discuss the potential value of regulators and the possible mechanism underlying the role of ferroptosis in the radiosensitization of NPC, in the hope that linking the mechanism of ferroptosis with the development of NPC will accelerate the development of novel ferroptosis-based targets and radiotherapy strategies in NPC.

In-silico analysis of ligand-receptor binding patterns of α-MMC, TCS and MAP30 protein to LRP1 receptor.

Alpha-momorcharin (α-MMC), trichosanthin (TCS), and momordica anti-HIV protein of 30 kD (MAP30) are potential anti-tumor drug candidates but have cytotoxicity to normal cells. The binding of these proteins to LRP1 receptor and the subsequent endocytosis are essential to their cytotoxicity, but this binding process remains largely unknown. This study, in-silico analysis of the binding patterns, was conducted via the protein-protein docking software, ZDOCK 3.0.2 package, to better understand the binding process. Specifically, α-MMC, TCS and MAP30 were selected and bound to binding subunits CR56 and CR17 of LRP1. After docking, the 10 best docking solutions are retained based on the default ZDOCK scores and used for structural assessment. Our results showed that, α-MMC bound to LRP1 stably at the amino acid residues 1-20, at which 8 residues formed 21 hydrogen bonds with 15 residues of CR56 and 10 residues formed 15 hydrogen bonds with 12 residues of CR17. In contrast, TCS and MAP30 bound mainly to LRP1 at the residues 1-57/79-150 and residues 58-102, respectively, which were functional domains of TCS and MAP30. Since residues 1-20 are outside the functional domain of α-MMC, α-MMC is considered more suitable to attenuate by mutating the receptor binding site. Thus, our analysis lays the foundation for future genetic engineering work on α-MMC, and makes important contributions to its potential clinical use in cancer treatment.

Alpha-momorcharin regulates cytokine expression and induces apoptosis in monocytes.

Background and aim: Alpha-momorcharin (α-MMC) is a type I ribosome-inactivating protein (RIP) that is purified from Momordica charantia. Despite its strong antitumor activities, α-MMC exerts the undesirable immunotoxicity effects of hypersensitivity or immunosuppression. Since α-MMC is a plant protein, its application in vivo can easily induce hypersensitivity, but its immunosuppressive mechanism is still unclear. Materials and methods: The toxicity of α-MMC to peripheral blood cells and the cytokine expression in peripheral blood mononuclear cells (PBMCs) and spleen immune cells were measured in rats. For further confirmation, experiments were performed in vitro with the mononuclear cell line THP-1, B lymphocyte cell line WIL2-S and T lymphocyte cell line Jurkat. Results: High doses of α-MMC (3.0 mg/kg) resulted in weight loss in rats, a decreased percentage of monocytes, and increased percentages of eosinophils and basophils. Both high-dose and low-dose (1.0 mg/kg) α-MMC inhibited cytokine expression in PBMCs and increased cytokine expression in spleen T cells. In in vitro, α-MMC mainly acted on THP-1 cells, with effects including high dose-induced apoptosis and low dose-induced regulation of inhibitory cytokine expression. Conclusions: The action of α-MMC on immune cells mainly affects monocytes, thereby eliciting its immunosuppressive effect. Its mode of action is to guide functional immunosuppressive regulation at low doses and induce apoptosis at high doses. As the monocytes would be recruited into tumor tissues and are polarized into tumor-associated macrophages, the selective cytotoxicity and cytokine release regulation of α-MMC in monocytes may be an important mechanism of its antitumor effects.

[Alpha-momordicin Regulates Hepatocyte Cytokine Expression].

OBJECTIVE: To investigate the regulation effect of α-momordicin (α-MMC) on the synthesis and secretion of cytokines in hepatocytes cells. METHODS: Hepatocytes L02 were treated with 189 µg/mL α-MMC with culture supernatant and lysate samples were harvested in different timepoint. Expressions of T-helper 17 (TH17) cytokine profile in samples were detected by the Bio-Plex 200 suspension chip assay system. RESULTS: Compared with 0 h, after the α-MMC treatment of L02 hepatocytes for 2 h, 4 h and 8 h, the intracellular synthesis of cytokines interleukin (IL)-1b, IL-6, IL-17A, IL-31, IL-33, soluble CD40 ligand (sCD40L), tumor necrosis factor-α (TNF-α) were all significantly decreased (P<0.05), and IL-6, IL-4, IL-17A, and sCD40L secreted into the extracellular fluid also decreased significantly (P<0.05). CONCLUSION: α-MMC can significantly inhibit the synthesis and secretion of cytokines such as IL-6, IL-17A and TNF-α in hepatocytes, which may become a side effect of its anti-tumor application.

LRP1 receptor-mediated immunosuppression of α-MMC on monocytes.

Alpha-MMC is a type I ribosome-inactivating protein purified from bitter gourd that has strong anti-tumour and antiviral activity. Alpha-MMC also has immunosuppressive effects, but the mechanism of these immunosuppressive effects remains unclear. It is reported that the binding of α-MMC to its specific cell membrane LRP1 receptor is key to its biological effects. In this study, we investigated the effect of α-MMC on cytotoxicity and cytokine release regulation in three immune cells, human monocyte THP-1 cells, B-lymphocyte WIL2 cells and T-lymphocyte H9 cells, and explored the correlation between this effect and LRP1 receptor distribution on these three cell types. We demonstrate that α-MMC has a significant effect of apoptosis induction and cytokine release in THP-1 cells but has no effect on WIL2-S and H9 cells. Specifically, at a non-cytotoxic dose (80 µg/ml), α-MMC regulates THP-1 cells by inhibiting IL-1ß, IL-2, IL-8, IL-9, IL-12, MIP-1α/ß, MCP-1 and TNF-α expression and enhancing IL-1ra and RANTES expression, resulting in the inhibition of cellular immune function. Subsequent experiments showed that the cytokine expression regulated by α-MMC can be blocked by silencing the LRP1 receptor of α-MMC. Further research indicated that phosphorylation of 9 signalling proteins of the MAPK pathway was significantly regulated by α-MMC and was blocked by LRP1 silencing. We conclude that the regulation of cytokine expression induced by α-MMC in monocyte THP-1 cells is mediated by the LRP1 receptor, likely via the MAPK signalling pathway. Our results suggest that the inhibition effect on monocytes/macrophages mediates the immunosuppressive function of α-MMC. Due to the selective cytotoxicity and cytokine release regulation of α-MMC in monocytes/macrophages, α-MMC may be used for killing Tumour-Associated Macrophages (M2 subtypes) or inhibiting their cytokine release in the tumour microenvironment.