Macrophage inflammatory protein(MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand(CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activatedprotein-kinase...Macrophage inflammatory protein(MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand(CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activatedprotein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation.展开更多
Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:...Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.展开更多
BACKGROUND Inflammatory bowel disease（IBD） is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial...BACKGROUND Inflammatory bowel disease（IBD） is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial effect of Toxo ROP16Ⅰ/Ⅲ-induced M2 phynotype macrophages in homeostasis of IBDs through downregulation of M1 inflammatory cells.METHODS RAW264.7 macrophages stimulated by lipopolysaccharide（LPS）（M1 cells） were co-cultured with Caco-2 cells as an inflammatory model of IBD in vitro.The expression of Toxo ROP16Ⅰ/Ⅲ was observed in RAW264.7 macrophages that were transfected with p EGFP-rop16Ⅰ/Ⅲ.The phenotypes of M2 and M1 macrophage cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction and the expression of tumor necrosis factor（TNF）-α,interleukin（IL）-1β,IL-6,transforming growth factor（TGF）-β1,IL-10,inducible nitric oxide synthase（i NOS）,and arginase-1（Arg-1） was detected.The expression of i NOS,Arg-1,signal transducer and activator of transcription 3（Stat3）,p-Stat3,Stat6,pStat6,programmed death ligand-2（PD-L2）,caspase-3,-8,and-9 was analyzed by Western blotting,and Griess assays were performed to detect nitric oxide（NO）.TNF-α,IL-1β,IL-6,TGF-β1,and IL-10 expression in the supernatants was detected by enzyme-linked immunosorbent assay,and Caco-2 cell apoptosis was determined by flow cytometry after mixing M1 cells with M2 cells in a Caco-2 cell co-culture system.RESULTS M1 cells exhibited significantly increased production of i NOS,NO,TNF-α,IL-1β,and IL-6,while Toxo ROP16Ⅰ/Ⅲ induced macrophage bias to M2 cells in vitro,showing increased expression of Arg-1,IL-10 and TGF-β1 and elevated production of p-Stat3 and p-Stat6.The mixed M1 and M2 cell culture induced by Toxo ROP16 Ⅰ/Ⅲ exhibited decreased production of NO and i NOS and upregulated expression of Arg-1 and PD-L2.Accordingly,Caco-2 cells became apoptotic,and apoptosis-associated proteins such as caspase-3,-8 and-9 were dampened during co-culture of M1 and M2 cells.Flow cytometry analysis showed that co-culture of M1 cells with Caco-2 cells facilitated the apoptosis of Caco-2 cells,but co-culture of M1 and M2 cells alleviated Caco-2 cell apoptosis.CONCLUSION Toxo ROP16 Ⅰ/Ⅲ-induced M2 macrophages inhibited apoptosis of Caco-2 cells caused by M1 macrophages.This finding may help gain a better understanding of the underlying mechanism and represent a promising therapeutic strategy for IBDs.展开更多
Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain re...Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.展开更多
AIM： To explore the expression of macrophage inflammatory protein-1α （MIP-1α） in Kupffer cells （KCs） following liver ischemia/reperfusion injury IRI in rats. METHODS： Forty male SD rats were divided randomly i...AIM： To explore the expression of macrophage inflammatory protein-1α （MIP-1α） in Kupffer cells （KCs） following liver ischemia/reperfusion injury IRI in rats. METHODS： Forty male SD rats were divided randomly into five groups. A model of partial warm ischemia/ reperfusion injury in the rat liver was established. KCs were isolated and incubated one hour, six hours, 12 h, and 24 h after the reperfusion. Tumor necrosis factor alpha （TNF-α） and interleukin-lbeta （IL-1β） in the supernatants were measured by ELISA. MIP-1α in KCs was detected by immunocytochemical and RT-PCR. RESULTS： No or few MIP-1α protein and mRNA were expressed in the KCs of the control group. Its expression in the IRI group had a significant increase after the reperfusion （P 〈 0.05）, which was contrary to the control group. CONCLUSION： The active behavior of the MIP-1α gene in KCs following liver ischemia/reperfusion injury is assumed to be one of the major causes for the hepatic ischemia/reperfusion injury.展开更多
Background/Aims: The objective of this study is to measure macrophage inflammatory protein one beta (MIP-1β), mean platelet volume (MPV) and platelet distribution width (PDW) to evaluate their usefulness in the diagn...Background/Aims: The objective of this study is to measure macrophage inflammatory protein one beta (MIP-1β), mean platelet volume (MPV) and platelet distribution width (PDW) to evaluate their usefulness in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Materials and Methods: This study comprised 41 cirrhotic patients with ascites. MPV, PDW and MIP-1β were measured in serum and ascitic fluid. Results: A significant increase MPV, PDW, C-reactive Protein (CRP) and white blood cell was observed in SBP group compared to non SBP (P ≤ 0.001, P = 0 β was significantly in-creased in ascitic fluid in patients with SBP versus non SBP (P ≤ 0.001). At cutoff value of 8.3 fl MPV had 85.7% sensitivity and 75% specificity (AUC = 0.876) for diagnosis of SBP. At cutoff value of 15.4 PDW had 90.4% sensitivity and 55% specificity (AUC = 0.762). At cutoff value of 121.9 pg/ml MIP-1β in ascitic fluid had 76.1% sensitivity and 100% specificity (AUC = 0.881) for detecting SBP. Conclusion: MIP-1β and platelet indices are useful marker in the diagnosis of SBP in cirrhotic patients. Combined measurement of MIP-1β in serum and ascitic fluid had 100% sensitivity and specificity for diagnosis of SBP.展开更多
目的探究2型糖尿病并发骨质疏松患者血清白脂素(Asprosin)、巨噬细胞炎症蛋白-1β(macrophageinflammato-ry protein-1β,MIP-1β)水平与骨密度及骨代谢指标的相关性。方法选取2022年4月~2023年4月在承德市中心医院就诊的172例2型糖尿...目的探究2型糖尿病并发骨质疏松患者血清白脂素(Asprosin)、巨噬细胞炎症蛋白-1β(macrophageinflammato-ry protein-1β,MIP-1β)水平与骨密度及骨代谢指标的相关性。方法选取2022年4月~2023年4月在承德市中心医院就诊的172例2型糖尿病患者为研究对象,并根据骨密度值结果分为2型糖尿病组(n=103)和2型糖尿病并发骨质疏松组(n=69);采用ELISA法测定血清Asprosin,MIP-1β水平;Pearson法分析血清Asprosin,MIP-1β表达水平与骨密度的相关性;Logistic回归分析2型糖尿病并发骨质疏松的影响因素;受试者工作特征(ROC)曲线分析血清Asprosin,MIP-1β水平对2型糖尿病并发骨质疏松的预测价值。结果与2型糖尿病组比,2型糖尿病并发骨质疏松组患者血清β-CTX(0.48±0.08ng/ml vs 0.42±0.04ng/ml),Asprosin(2.26±0.56ng/ml vs 1.65±0.36ng/ml),MIP-1β(26.01±6.43pg/ml vs 19.46±4.27pg/ml)水平均显著升高,骨密度(0.67±0.13g/cm2 vs 0.84±0.17g/cm2),BGP(8.33±1.23ng/ml vs 9.54±1.42ng/ml),T-P1NP(30.38±3.27ng/ml vs 32.49±3.29ng/ml)水平降低,差异具有统计学意义(t=6.501,8.699,8.032,7.039,5.773,4.133,均P<0.05);Pearson法分析显示,2型糖尿病并发骨质疏松组患者血清Asprosin,MIP-1β水平均与骨密度呈负相关(r=-0.484,-0.498,均P<0.05);Logistic回归分析显示血清Asprosin,MIP-1β水平均为影响2型糖尿病并发骨质疏松发生的独立危险因素(均P<0.05);ROC曲线分析显示,血清Asprosin,MIP-1β水平预测2型糖尿病患者并发骨质疏松的AUC分别为0.768,0.704,联合预测的AUC为0.859,优于二者单独预测(Z=1.812,2.895,均P<0.05)。。结论2型糖尿病患者并发骨质疏松患者血清Asprosin,MIP-1β水平显著升高,二者水平与骨密度密切相关,血清Asprosin,MIP-1β是2型糖尿病发生骨质疏松的独立危险因素,二者联合检测对疾病发展有较高的预测价值。展开更多
Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 ph...Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.展开更多
In order to study whether the endothelial cells (ECs) with lipid peroxidation induced by diamide can express and secrete macrophage inflammatory protein 1α (MIP-1α), the expression of MIP-1α protein in the cells wa...In order to study whether the endothelial cells (ECs) with lipid peroxidation induced by diamide can express and secrete macrophage inflammatory protein 1α (MIP-1α), the expression of MIP-1α protein in the cells was detected by cell enzyme-linked immunosorbent assay (ELISA) and that of MIP-1α mRNA was determined by cell in situ hybridization and nuclease S1 protection assay after the ECs were exposed to different concentrations of diamide for 4 h. The chemotactic activity of MIP-1α was tested by micropore filter method using modified Boyden chambers. Cell ELISA showed that the expression of MIP-1α protein in endothelial cells exposed to 1 μmol/L, 5 μmol/L and 10 μmol/L diamide was 1.9-fold, 2.3-fold and 1.7-fold respectively as much as that in the control cells, which was statistically significant by analysis of variance. In situ hybridization revealed that the mRNA expression of ECs treated with 1 μmol/L, 5 μmol/L and 10 μmol/L diamide was 1 3-fold, 3.0-fold and 1.7-fold as much as that in the control group, which had statistical significance ( F =188.93, P <0.01). The mRNA expression in 5 μmol/L dimide treated ECs, measured by nuclease S1 protection assay, was 3.4-fold as much as that in the control group( t =8 70, P <0 05). Chemotactic response(99.50±4.31 μm) to the culture medium conditioned by 5 μmol/L diamide treated ECs , which was stronger than that(66.47±3.25 μm) conditioned by the ECs ( F =404.31, P <0.05), was significantly decreased ( F =192.25, P <0.05) after adding MIP-1α antibody. It suggests that diamide, a lipid peroxidation inducer, could stimulate ECs to produce high level of MIP-1α, and might play an important role in atherogenesis by promoting the migration of peripheral blood monocytes into arterial intima.展开更多
Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the...Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.展开更多
Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than c...Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration,and rarely take Porphyromonas gingivalis(Pg),the keystone pathogen responsible for periodontal tissue destruction,into consideration.Though M2 macrophage-derived exosomes(M2-EXO)show promise in tissue regeneration,the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects,restricting the regeneration potential of M2-EXO.Here,exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1(Ckip-1),a versatile player involved in various biological processes.Ckip-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting effect.Further,exosomes derived from Ckip-1-silenced macrophages(sh-Ckip-1-EXO)rescue Pg-suppressed cementoblast mineralization and cementogenesis.Mechanismly,sh-Ckip-1-EXO delivers Let-7f-5p targeting and silencing Ckip-1,a negative regulator also for cementum formation and cementoblast mineralization.More deeply,downregulation of Ckip-1 in cementoblasts by exosomal Let-7f-5p activates PGC-1α-dependent mitochondrial biogenesis.In all,this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.展开更多
基金Supported by the State 12th 5-Year Plan S&T Projects of China,No.2012ZX10002007National Natural Science Foundation of China,No.81272679,No.81470851
文摘Macrophage inflammatory protein(MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand(CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activatedprotein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation.
基金supported by Natural Science Foundation of Hainan Province(820MS135)Hainan Provincial Health Commission 2023 Provincial Key Clinical Discipline(Clinical Medical Center)Construction Unit Fund Project(Qiongwei Yihan[2022]No.341)Hainan Provincial Health Technology Innovation Joint Project(WSJK2024MS209).
文摘Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.
基金Supported by the National Natural Science Foundation of China,No.81471983the Key Research and Development Plan Project of Anhui Province,Department of Science and Technology 2019,No.201904a07020043+1 种基金the Key Project of Natural Science Research in the Universities of Anhui Provence,No.KJ2017A202the Research Fund Project of Anhui Institute of Transforming Medicine,No.2017zhyx04
文摘BACKGROUND Inflammatory bowel disease（IBD） is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial effect of Toxo ROP16Ⅰ/Ⅲ-induced M2 phynotype macrophages in homeostasis of IBDs through downregulation of M1 inflammatory cells.METHODS RAW264.7 macrophages stimulated by lipopolysaccharide（LPS）（M1 cells） were co-cultured with Caco-2 cells as an inflammatory model of IBD in vitro.The expression of Toxo ROP16Ⅰ/Ⅲ was observed in RAW264.7 macrophages that were transfected with p EGFP-rop16Ⅰ/Ⅲ.The phenotypes of M2 and M1 macrophage cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction and the expression of tumor necrosis factor（TNF）-α,interleukin（IL）-1β,IL-6,transforming growth factor（TGF）-β1,IL-10,inducible nitric oxide synthase（i NOS）,and arginase-1（Arg-1） was detected.The expression of i NOS,Arg-1,signal transducer and activator of transcription 3（Stat3）,p-Stat3,Stat6,pStat6,programmed death ligand-2（PD-L2）,caspase-3,-8,and-9 was analyzed by Western blotting,and Griess assays were performed to detect nitric oxide（NO）.TNF-α,IL-1β,IL-6,TGF-β1,and IL-10 expression in the supernatants was detected by enzyme-linked immunosorbent assay,and Caco-2 cell apoptosis was determined by flow cytometry after mixing M1 cells with M2 cells in a Caco-2 cell co-culture system.RESULTS M1 cells exhibited significantly increased production of i NOS,NO,TNF-α,IL-1β,and IL-6,while Toxo ROP16Ⅰ/Ⅲ induced macrophage bias to M2 cells in vitro,showing increased expression of Arg-1,IL-10 and TGF-β1 and elevated production of p-Stat3 and p-Stat6.The mixed M1 and M2 cell culture induced by Toxo ROP16 Ⅰ/Ⅲ exhibited decreased production of NO and i NOS and upregulated expression of Arg-1 and PD-L2.Accordingly,Caco-2 cells became apoptotic,and apoptosis-associated proteins such as caspase-3,-8 and-9 were dampened during co-culture of M1 and M2 cells.Flow cytometry analysis showed that co-culture of M1 cells with Caco-2 cells facilitated the apoptosis of Caco-2 cells,but co-culture of M1 and M2 cells alleviated Caco-2 cell apoptosis.CONCLUSION Toxo ROP16 Ⅰ/Ⅲ-induced M2 macrophages inhibited apoptosis of Caco-2 cells caused by M1 macrophages.This finding may help gain a better understanding of the underlying mechanism and represent a promising therapeutic strategy for IBDs.
文摘Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.
文摘AIM： To explore the expression of macrophage inflammatory protein-1α （MIP-1α） in Kupffer cells （KCs） following liver ischemia/reperfusion injury IRI in rats. METHODS： Forty male SD rats were divided randomly into five groups. A model of partial warm ischemia/ reperfusion injury in the rat liver was established. KCs were isolated and incubated one hour, six hours, 12 h, and 24 h after the reperfusion. Tumor necrosis factor alpha （TNF-α） and interleukin-lbeta （IL-1β） in the supernatants were measured by ELISA. MIP-1α in KCs was detected by immunocytochemical and RT-PCR. RESULTS： No or few MIP-1α protein and mRNA were expressed in the KCs of the control group. Its expression in the IRI group had a significant increase after the reperfusion （P 〈 0.05）, which was contrary to the control group. CONCLUSION： The active behavior of the MIP-1α gene in KCs following liver ischemia/reperfusion injury is assumed to be one of the major causes for the hepatic ischemia/reperfusion injury.
文摘Background/Aims: The objective of this study is to measure macrophage inflammatory protein one beta (MIP-1β), mean platelet volume (MPV) and platelet distribution width (PDW) to evaluate their usefulness in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Materials and Methods: This study comprised 41 cirrhotic patients with ascites. MPV, PDW and MIP-1β were measured in serum and ascitic fluid. Results: A significant increase MPV, PDW, C-reactive Protein (CRP) and white blood cell was observed in SBP group compared to non SBP (P ≤ 0.001, P = 0 β was significantly in-creased in ascitic fluid in patients with SBP versus non SBP (P ≤ 0.001). At cutoff value of 8.3 fl MPV had 85.7% sensitivity and 75% specificity (AUC = 0.876) for diagnosis of SBP. At cutoff value of 15.4 PDW had 90.4% sensitivity and 55% specificity (AUC = 0.762). At cutoff value of 121.9 pg/ml MIP-1β in ascitic fluid had 76.1% sensitivity and 100% specificity (AUC = 0.881) for detecting SBP. Conclusion: MIP-1β and platelet indices are useful marker in the diagnosis of SBP in cirrhotic patients. Combined measurement of MIP-1β in serum and ascitic fluid had 100% sensitivity and specificity for diagnosis of SBP.
文摘目的探究2型糖尿病并发骨质疏松患者血清白脂素(Asprosin)、巨噬细胞炎症蛋白-1β(macrophageinflammato-ry protein-1β,MIP-1β)水平与骨密度及骨代谢指标的相关性。方法选取2022年4月~2023年4月在承德市中心医院就诊的172例2型糖尿病患者为研究对象,并根据骨密度值结果分为2型糖尿病组(n=103)和2型糖尿病并发骨质疏松组(n=69);采用ELISA法测定血清Asprosin,MIP-1β水平;Pearson法分析血清Asprosin,MIP-1β表达水平与骨密度的相关性;Logistic回归分析2型糖尿病并发骨质疏松的影响因素;受试者工作特征(ROC)曲线分析血清Asprosin,MIP-1β水平对2型糖尿病并发骨质疏松的预测价值。结果与2型糖尿病组比,2型糖尿病并发骨质疏松组患者血清β-CTX(0.48±0.08ng/ml vs 0.42±0.04ng/ml),Asprosin(2.26±0.56ng/ml vs 1.65±0.36ng/ml),MIP-1β(26.01±6.43pg/ml vs 19.46±4.27pg/ml)水平均显著升高,骨密度(0.67±0.13g/cm2 vs 0.84±0.17g/cm2),BGP(8.33±1.23ng/ml vs 9.54±1.42ng/ml),T-P1NP(30.38±3.27ng/ml vs 32.49±3.29ng/ml)水平降低,差异具有统计学意义(t=6.501,8.699,8.032,7.039,5.773,4.133,均P<0.05);Pearson法分析显示,2型糖尿病并发骨质疏松组患者血清Asprosin,MIP-1β水平均与骨密度呈负相关(r=-0.484,-0.498,均P<0.05);Logistic回归分析显示血清Asprosin,MIP-1β水平均为影响2型糖尿病并发骨质疏松发生的独立危险因素(均P<0.05);ROC曲线分析显示,血清Asprosin,MIP-1β水平预测2型糖尿病患者并发骨质疏松的AUC分别为0.768,0.704,联合预测的AUC为0.859,优于二者单独预测(Z=1.812,2.895,均P<0.05)。。结论2型糖尿病患者并发骨质疏松患者血清Asprosin,MIP-1β水平显著升高,二者水平与骨密度密切相关,血清Asprosin,MIP-1β是2型糖尿病发生骨质疏松的独立危险因素,二者联合检测对疾病发展有较高的预测价值。
基金supported by grants from the Research Unit Project of Chinese Academy of Medical Sciences(No.2019-I2M-5-030)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022002A)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H030009).
文摘Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.
文摘In order to study whether the endothelial cells (ECs) with lipid peroxidation induced by diamide can express and secrete macrophage inflammatory protein 1α (MIP-1α), the expression of MIP-1α protein in the cells was detected by cell enzyme-linked immunosorbent assay (ELISA) and that of MIP-1α mRNA was determined by cell in situ hybridization and nuclease S1 protection assay after the ECs were exposed to different concentrations of diamide for 4 h. The chemotactic activity of MIP-1α was tested by micropore filter method using modified Boyden chambers. Cell ELISA showed that the expression of MIP-1α protein in endothelial cells exposed to 1 μmol/L, 5 μmol/L and 10 μmol/L diamide was 1.9-fold, 2.3-fold and 1.7-fold respectively as much as that in the control cells, which was statistically significant by analysis of variance. In situ hybridization revealed that the mRNA expression of ECs treated with 1 μmol/L, 5 μmol/L and 10 μmol/L diamide was 1 3-fold, 3.0-fold and 1.7-fold as much as that in the control group, which had statistical significance ( F =188.93, P <0.01). The mRNA expression in 5 μmol/L dimide treated ECs, measured by nuclease S1 protection assay, was 3.4-fold as much as that in the control group( t =8 70, P <0 05). Chemotactic response(99.50±4.31 μm) to the culture medium conditioned by 5 μmol/L diamide treated ECs , which was stronger than that(66.47±3.25 μm) conditioned by the ECs ( F =404.31, P <0.05), was significantly decreased ( F =192.25, P <0.05) after adding MIP-1α antibody. It suggests that diamide, a lipid peroxidation inducer, could stimulate ECs to produce high level of MIP-1α, and might play an important role in atherogenesis by promoting the migration of peripheral blood monocytes into arterial intima.
文摘Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.
基金supported by the National Natural Science Foundation of China(No.82370967,No.82170963)。
文摘Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration,and rarely take Porphyromonas gingivalis(Pg),the keystone pathogen responsible for periodontal tissue destruction,into consideration.Though M2 macrophage-derived exosomes(M2-EXO)show promise in tissue regeneration,the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects,restricting the regeneration potential of M2-EXO.Here,exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1(Ckip-1),a versatile player involved in various biological processes.Ckip-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting effect.Further,exosomes derived from Ckip-1-silenced macrophages(sh-Ckip-1-EXO)rescue Pg-suppressed cementoblast mineralization and cementogenesis.Mechanismly,sh-Ckip-1-EXO delivers Let-7f-5p targeting and silencing Ckip-1,a negative regulator also for cementum formation and cementoblast mineralization.More deeply,downregulation of Ckip-1 in cementoblasts by exosomal Let-7f-5p activates PGC-1α-dependent mitochondrial biogenesis.In all,this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.
