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Regulation of the macrophage-related inflammatory microenvironment for atherosclerosis treatment and angiogenesis via anti-cytokine agents

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Nano Research 2022年第8期15卷 7342-7354页

作者： Hongji Pu Minghua Yao Zhaoyu Wu Zhijue Xu Chaoyi Cui Renhua Huang Muhammad Shafiq Weimin Li Xinwu Lu Bo Li Department of Vascular Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Ultrasound Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200040China Department of Radiation Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Chemical Engineering Faculty of EngineeringGraduate SchoolKyushu University744 MotookaNishi-kuFukuoka 819-0395Japan

macrophages-mediated atherosclerosis(AS)is an inflammatory disease and the most common cause of *** the progress of basic and clinical research,anti-cytokine therapy has garnered considerable attention of the research community for the regulation of the inflammatory microenvironment for AS *** of their promising potential,primary clinical trials have revealed that anti-cytokine drugs exhibit poor selectivity and thus affect other parts of the immune system,especially during long-term *** circumvent these limitations,herein we exploited mesoporous silica nanoparticles(MSNs)with a pore size of 15.5 nm as carriers for the anti-interleukin-1β(anti-IL-1β)delivery to be the anti-cytokine *** vitro mechanistic studies indicated that the MSNs@anti-IL-1βcan regulate the macrophage-related inflammatory microenvironment,promote the viability of vascular endothelial cells(vECs),and reduce proliferation and phenotypic switching of vascular smooth muscle cells(vSMCs).In vivo evaluation further revealed that the MSNs@anti-IL-1βwere preferentially accumulated in macrophages,impeding the AS progress by maintaining the endothelium integrity and inhibiting the vSMCs ***,MSNs@antiIL-1βinduced neovascularization and improved hindlimb ischemia *** together,these MSNs affording the sustained release of anti-cytokine agents may have broad implications for the clinical management of the AS,including the reduction of the AS progression and alleviation of the ischemia.

关键词： atherosclerosis inflammatory response nanocarriers macrophage endothelial cells

Degradation particles derived from high-purity magnesium inhibit osteogenic differentiation through regulation of macrophage polarization

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Journal of Materials Science & Technology 2023年第8期139卷 113-119页

作者： Yu Sun Han Yu Hongzhou Peng Xinbao Kang Zhaoxiang Peng Xieping Dong Wenhui Wang Yang Song Xiaonong Zhang State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Orthopaedic Surgery Ningbo Medical Treatment Center Lihuili HospitalNingbo 315040China Department of Orthopaedic Surgery Jiangxi People’s HospitalNanchang 330006China Suzhou Origin Medical Technology Co.Ltd. Jiangsu 215513China

Magnesium(Mg)and its alloys have great potential as orthopedic implant candidates,which could release various bioactive substances during *** particles(DPs)are one of the degradation products,but the osteoimmunology effects are still *** this study,the effect of DPs on the polar-ization of macrophages and their release of cytokines was *** results verify that excessive generation of DPs from biodegradable Mg can induce macrophages to realize polarization of proinflamma-tory M1 ***,macrophages secrete proinflammatory cytokines to inhibit the osteogenic differentiation of rat bone marrow stem cells(rBMSCs).This suggests that the effects of DPs should be considered when evaluating Mg-based *** continuously produced with the degradation of Mg-based implants may influence osseointegration.

关键词： Magnesium Degradation particles macrophage Phagocytosis Osteoimmunology

Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo

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Journal of Environmental Sciences 2021年第3期33卷 236-247页

作者： Qidong Ren Xinni Xie Yue Tang Qing Hu Yuguo Du State Key Laboratory of Environmental Chemistry and Eco-Toxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China School of Environmental Science and Engineering Southern University of Science and TechnologyShenzhen 518055China

The biosafety of methyl tertiary-butyl ether(MTBE),mainly used as a gasoline additive,has long been a contentious *** addition to its routine toxicities,MTBE has been demonstrated to disrupt glucose and lipid metabolism and contribute to the development of type2 diabetes as well as *** one of the morbidities related to dyslipidemia,atherosclerosis is worthy of being investigated under MTBE *** foam cells derived from macrophages play pivotal roles during atherosclerosis development,we studied the effects of MTBE on macrophages in vitro and assessed the effect of MTBE on atherosclerosis plaque formation with the ApoE^(-/-)mouse model in uiuo for the first *** results demonstrated that exposure to MTBE at environmentally relevant concentrations decreased the expression of ABCA1 and ABCG1,which are responsible for macrophage cholesterol efflux,at both mRNA and protein levels in THP-1 ***,treatment with MTBE inhibited the transport of cholesterol from macrophages to High-density ***^(-/-)mice exposed to MTBE at environmentally relevant concentrations(100,1000μg/kg)displayed significant increases in lesion area in the aorta and aortic root compared to vehicletreated *** analysis indicated that MTBE exposure enhanced the macrophagespecific marker Mac-2 contents within plaques in the aortic root,implying that MTBE could promote macrophage-derived foam cell formation and thus accelerate atherosclerosis plaque *** for the first time demonstrated the pro-atherogenic effect of MTBE via eliciting disruption of macrophage cholesterol efflux and accelerating foam cell formation and atherosclerosis plaque development.

关键词： Methyl tertiary–butyl ether(MTBE) macrophage cholesterol efflux ApoE^(-/-)mouse Atherosclerosis

Unique regulation of TiO_(2)nanoporous topography on macrophage polarization via MSC-derived exosomes

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Regenerative Biomaterials 2023年第1期10卷 549-560页

作者： Jinjin Wang Yazheng Wang Yi Li Yide He Wen Song Qintao Wang Yumei Zhang Chenyang He State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Department of PeriodontologySchool of StomatologyThe Fourth Military Medical UniversityXi’anShannxi Province 710032China State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology Department of ProsthodonticsSchool of StomatologyThe Fourth Military Medical UniversityXi’anShannxi Province 710032China Department of Surgical Oncology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShannxi Province 710004China

The comprehensive recognition of communications between bone marrow mesenchymal stem cells(bm-MSCs)and macrophages in the peri-implant microenvironment is crucial for implantation *** previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage ***,cell communication is commutative and *** the immune regulatory properties of MSCs have become increasingly prominent,whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is *** further illuminate the communications between bm-MSCs and macrophages,the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages,and by blocking exosome secretion or extracting the purified exosomes to induce independently,we bidirectionally confirmed that under the influence of TiO_(2)nanoporous topography with 80-100 nm tube diameters,bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages,adversely affecting the osteogenic microenvironment around the *** finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.

关键词： nanoporous topography bone marrow mesenchymal stem cell exosome immunomodulatory effect macrophage

Surface charge of PLA microparticles in regulation of antigen loading,macrophage phagocytosis and activation,and immune effects in vitro

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Particuology 2014年第6期12卷 74-80页

作者： Yuying Liu Xiaoming Chen Lianyan Wang Tingyuan Yang Qipeng Yuan Guanghui Ma National Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of Sciences State Key Laboratory of Chemical Resource Engineering College of Life Science and TechnologyBeijing University of Chemical Technology University of Chinese Academy of Sciences

The use of microparticles（MPs） as adjuvants has attracted increasing interest in vaccine delivery *** physiochemical characteristics of MPs including hydrodynamic size,surface properties,and morphology can regulate the immune *** charge is an important characteristic of MPs,but how it affects their adjuvanticity remains *** this study,we prepared uniform-sized polylactide MPs coated with various polymers of different positive charge,and investigated how the surface charge affected antigen loading and macrophage phagocytosis and activation in vitro.A higher surface charge greatly enhanced antigen loading and antigen internalization into macrophages,promoted the expression of MHC 11 and CD80,and increased the secretion level of *** together,these results indicated that surface charge was an important parameter for improving the adjuvanticity of MPs.

关键词： Microparticle(MP) macrophage Surface charge Antigen loading Phagocytosis Activation

macrophage-derived matrix metalloproteinase-1 enhances aortic aneurysm formation in transgenic rabbits

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The Journal of Biomedical Research 2019年第4期33卷 271-279页

作者： Manabu Niimi Kazutoshi Nishijima Shuji Kitajima Fumikazu Matsuhisa Kaneo Satoh Hirokazu Yamazaki Jifeng Zhang Y. Eugene Chen Jianglin Fan Department of Molecular Pathology Graduate School of MedicineUniversity of YamanashiYamanashi 409-3898Japan Animal Research Laboratory Bioscience Education-Research Support CenterAkita UniversityAkita 010-8502Japan Analytical Research Center for Experimental Sciences Saga UniversitySaga 840-8502Japan Department of Laboratory Medicine Graduate School of MedicineUniversity of YamanashiYamanashi 409-3898Japan Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Medical CenterAnn ArborMI 48109USA School of Biotechnology and Health Sciences Wuyi UniversityJiangmenGuangdong 529020China

Increased expression of matrix metalloproteinase-1(MMP-1)has been observed in the lesions of atherosclerosis and aneurysms;however,it is not fully understood whether macrophage-derived MMP-1 affects these *** investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases,we generated transgenic(Tg)rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/*** rabbits exhibited no visible abnormalities throughout their *** blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg *** the first experiment,Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks,and aortic and coronary atherosclerosis were *** gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits,but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic *** the second experiment,we generated aortic aneurysms by incubating with *** with non-Tg rabbits,Tg rabbits exhibited a significantly greater aortic *** macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and *** results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.

关键词： matrix metalloproteinase-1 macrophage atherosclerosis aneurysm transgenic rabbit

macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy?

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World Journal of Diabetes 2024年第9期15卷 1847-1852页

作者： Saeed Mohammadi Ahmed Al-Harrasi Natural and Medical Sciences Research Center University of NizwaNizwa 616Oman Department of Biological Sciences and Chemistry University of NizwaNizwa 616Oman

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)*** et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse *** suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised *** also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic *** play crucial roles in DCM *** hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart ***,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory *** compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 *** studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

关键词： Diabetic cardiomyopathy macrophage Dipeptidyl peptidase-4 inhibitor Teneligliptin NLRP3 inflammasome Glucagon-like peptide-1

Inhibitory Effects of Lanthanum on NF-κB Activation Induced by LPS in Mice macrophage

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Journal of Rare Earths 2005年第S1期23卷 513-517页

作者：汪泱郭菲赵萍谢安娄远蕾李国辉 Institute of Urology Nanchang University Nanchang 330006 China Burns Institute of Nanchang University Nanchang 330006 China Jiangxi Academy of Science 330006 China

Nuclear factor-κB(NF-κB), a transcription factor, which plays a pivotal role in the expression of a wide variety of genes, involves in systemic inflammatory response syndrome and is the new target for therapy. To explore the effects and mechanism of lanthanum on nuclear translocation of NF-κB in macrophage of mice(Mφ), fluorescent antibody technique, western blotting and ELISA(enzyme-linked immunosorbent assay) were employed. Mφ were divided into five groups at random: one was the control group, in which the cells were cultured in medium without any stimulation, one was LPS (lipopolysaccharide) group, in which the cells were incubated with 1 μg·ml -1 LPS for 30 min and one was LaCl_3 group, in which cells were incubated with 2.5 μm of lanthanum chloride for 30 min. The forth group was named as LaCl_3+LPS group, in which cells were incubated with 2.5 μm of lanthanum chloride for 30 min before stimulated with LPS(1 μg·ml -1, 30 min), and the fifth group was known as LaCl_3/LPS group, in which the cells were cultured in medium containing 2.5 μm of lanthanum chloride at first, then the cells were incubated with LPS(1 μg·ml -1, 30 min) after lanthanum chloride was removed from the media. The location of NF-κB p65 subunit (NF-κB/p65) in Mφ was detected by immunofluorescence and fluorescence microscope. The activation of NF-κB/P65 in nuclei was detected by TransAM TM NF-κB/P65 Transcription Factor assay kit. Meanwhile, the expression of NF-κB/p65 in nuclei and that of IκBα in cytoplasm were measured by Western blotting analysis. The majority of FITC-labeled NF-κB/p65 was located in the nuclei stimulated with LPS. However, there was less fluorescence seen in the nuclei of control group, LaCl_3 group, LaCl_3 + LPS group and LaCl_3/LPS group. Compared with LPS group, the IκBα protein level in cytoplasm increase in LaCl_3 group, LaCl_3+LPS group and LaCl_3/LPS group. The expression and activation of nuclei p65 protein decrease significantly in LaCl_3 group, LaCl_3+LPS group an

关键词： lanthanum lipopolysaccharides NF-κB macrophage rare earths

Effects of chlorogenic acid, an active compound activating calcineurin, purified from Flos Lonicerae on macrophage

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Acta Pharmacologica Sinica 2004年第12期25卷 119-123页

作者： He-zhen WU, Jing LUO, Yan-xia YIN, Qun WEI2 Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing 100875, China Department of Biochemistry and Molecular Biology Beijing Normal University

AIM: To investigate the activation of chlorogenic acid (CHA) purified from Flos Lonicerae to calcineurin and its effects on macrophage functions in vivo and in vitro. METHODS: According to the screening results that Flos Lonicerae could activate calcineurin, the active component which could activate calcineurin was purified from Flos Lonicerae by column chromatography on silica gel and identified as CHA. The activation of CHA on calcineurin had been validated with both p-NPP and P-labeled RII peptide as the substrates. The clearance of charcoal particles in 32 normal mice and the cytotoxicity of U937 to MCF-7 were used together to determine the effects of CHA on macrophage functions. RESULTS: CHA could activate calcineurin, and the concentration of CHA on maximal activating calcineurin was 282.5 μmol/L. CHA administration (10 mg/kg, ig×7 d) significantly enhanced the mac- rophage functions in normal mice. CHA (70.6, 141.2, and 282.5 μmol/L) obviously increased the cytotoxicity of U937 to MCF-7. CONCLUSION: CHA could activate calcineurin and enhance the macrophage functions in vivo and in vitro, and its functions in vivo may be realized via the signal pathways of calcineurin.

关键词： calcineurin macrophage chlorogenic acid Flos Lonicerae