Objective To investigate the role of calcium- and integrin-binding protein-1（CIB1） in oxidized lowdensity lipoprotein（OX-LDL） inhibiting migration of mouse macrophages. Methods To silence CIB1 express of mouse macrophages by RNA interference, then incubating mouse macrophages with OX-LDL, cell migration and cell spreading of mouse macrophages were analyzed. Results At 24-72h after macrophages transfected CIB1 siRNA, the express of CIB1 protein was restrained obviously. To silence CIB1 express could increase migration and spreading of mouse macrophages significantly. Conclusions CIB1 plays the important role in intracellular modulating mechanism of OX-LDL inhibiting mouse macrophages migration.
ObjectiveTo investigate the effect of curcumin on lipopolysaccharide (LPS)-induced inflammation and apoptosis in alveolar macrophage via microRNA-132 (miR-132)/high mobility group protein B1 (HMGB1).MethodsThe cultured mouse alveolar macrophage line (RAW264.7 cells) were divided into the control group, the LPS group, the LPS+50 μmol/L curcumin group, and the LPS+100 μmol/L curcumin group. Forty-eight hours after drug treatment, the levels of miR-132/HMGB1, inflammatory mediator and apoptotic were detected. Secondly, the empty vector, synthetic miR-132 mimics and inhibitors were transfected into another cultured mouse alveolar macrophage line (RAW264.7 cells) to detect the inflammation and apoptosis of alveolar macrophage after transfection.ResultsCompared with the control group, in the LPS group, the apoptosis of alveolar macrophage, the levels of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α, and the expression of miR-132 increased, while the expression of HMGB1 decreased (P<0.05); compared with the LPS group, in the two curcumin groups, the apoptosis of alveolar macrophage, the levels of IL-6, IL-8 and TNF-α, and the expression of miR-132 decreased, while the expression of HMGB1 increased (P<0.05); and the greater the drug concentration, the more obvious the effect (P<0.05). In addition, up-regulation of miR-132 reduced the expression of HMGB1 in alveolar macrophage, increased inflammatory factor, and induced apoptosis in alveolar macrophage; however, down-regulation of miR-132 increased the expression of HMGB1 in alveolar macrophage, reduced inflammatory factor, and inhibited apoptosis in alveolar macrophage (P<0.05).ConclusionCurcumin could decrease LPS-induced inflammation and apoptosis in alveolar macrophage via decreasing miR-132 and increasing HMGB1.
Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
Objective To explore the association of macrophages with carcinogenesis and development of gastric cancer. Method The related literatures at home and abroad were consulted and reviewed. Results The microenvironment of gastric cancer could induce the polarization of macrophages，and then the activated macrophages，especially the tumor associated macrophages，could in turn motivate the growth，invasion，and metastasis of tumor cells by secreting a series of active substances. Conclusions Macrophages，especially the tumor associated macrophages play an importantrole in the carcinogenesis and development of gastric cancer. Investigating the macrophages and their interaction with gastric cancer may lead to a profound understanding of carcinogenesis of gastric cancer as well as opening up a new prospectfor treatment.
ObjectiveTo understand the interplay between tumor-associated macrophages (TAMs) and T lymphocytes, as well as the effect on the pathogenesis of hepatocellular carcinoma (HCC) again, so that providing new ideas and methods for the immunotherapy of HCC.MethodSearched the literatures about the interplay between TAMs and T lymphocytes in HCC to analyze and summarize the relationship between TAMs and T lymphocytes in HCC.ResultsWhile TAMs and T lymphocytes themselves regulate the process of tumorigenesis and development, they also had a mutual regulatory mechanism to further promote the development of HCC.ConclusionsThere is an interaction between TAMs and T lymphocytes, and this interaction forms a vicious circle to a large extent and promotes the development of HCC. Recognizing and making rational use of this interaction can provide new ideas and methods for the future immunotherapy of HCC.
ObjectiveTo investigate the effect of graphene oxide (GO)-carboxymethyl chitosan (CMC) hydrogel loaded with interleukin 4 (IL-4) and bone morphogenetic protein 2 (BMP-2) on macrophages M2 type differentiation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).MethodsGO solution was mixed with CMC, then the phosphate buffered saline (PBS), IL-4, BMP-2, or IL-4+BMP-2 were added to prepare different GO-CMC hydrogel scaffolds with or without different cytokines under crosslinking agents. The characteristics of pure GO-CMC hydrogel were characterized by gross observation, scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR), and the CMC hydrogel was used as control. The sustained release of GO-CMC hydrogels with different cytokines was also tested. Macrophages were isolated and cultured from female Sprague Dawley rats aged 4-5 weeks, and then cultured with GO-CMC hydrogels with and without different cytokines, respectively. CD206 immunofluorescence staining was used to detect the differentiation of macrophages after 24 hours. The 3rd generation of rats BMSCs were cultured with GO-CMC hydrogels with and without different cytokines respectively for osteogenic induction. The early osteogenesis was observed by alkaline phosphatase (ALP) staining after 10 days, and the late osteogenesis was observed by alizarin red staining after 21 days.ResultsGenerally, GO-CMC hydrogel was brown and translucent. SEM showed that the pore diameter and wall thickness of GO-CMC hydrogel were similar to that of CMC hydrogel, but the inner wall roughness increased. FTIR test showed that CMC polymerized to form hydrogel. In vitro, the sustained release experiments showed that the properties of GO-CMC hydrogels loaded with different cytokines were similar. CD206 immunofluorescence detection showed that GO-CMC hydrogels could induce macrophages differentiation into M2-type. ALP and alizarin red staining showed that GO-CMC hydrogels could induce BMSCs osteogenic differentiation, in which GO-CMC hydrogel loaded with IL-4+BMP-2 showed the most significant effect (P<0.05).ConclusionThe GO-CMC hydrogel loaded with IL-4 and BMP-2 can induce macrophages differentiation into M2-type and enhance the ability of BMSCs with osteogenic differentiation in vitro, which provide a new strategy for bone defect repair and immune regulation.
ObjectiveTo investigate the effect of miR-190a-5p on the polarization of bone-marrow-derived macrophage (BMDM) induced by lipopolysaccharides to M1- and M2-types.MethodsBMDM (M1-type) induced by bacterial lipopolysaccharide was a M1 group. The macrophage M1-type interfered with negative control miRNA mimics was a NC group. miR-190a-5p mimics interfered with the M1-type of macrophages in the miR-190a-5p group. Morphological changes of macrophages were observed under a microscope, and the proportion of M2-type macrophages (CD206+, F4/80) was detected by flow cytometry. The mRNA expression levels of argininase-1 (Arg1), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), target gene C/EBPα and PU.1 were detected by fluorescence quantitative PCR to verify whether C/EBPα and PU.1 were potential target genes of miR-190a-5p. The expression of pathway proteins C/EBPα and PU.1 were detected by Western blotting.ResultsAfter miR-190a-5p mimics interfered with macrophage M1-type, the antenna of macrophages elongated and showed long cord M2-type cell morphological characteristics. miR-190a-5p mimics interfered with M1-type macrophages for 24 h, and the percentage of M2-type macrophages increased significantly (P<0.05). Effects of miR-190a-5p simulator on mRNA expression levels of M1-type macrophages included: the expression of iNOS and TNF-α was significantly decreased (P<0.05), the expression of Arg1 marked by M2 macrophages was significantly increased (P<0.05), and the mRNA expression levels of target genes C/EBPα and PU.1 were significantly decreased (P<0.05). Western blotting results showed that the overexpression of miR-190a-5p significantly inhibited the protein expressions of C/EBPα and PU.1, while the miR-190a-5p inhibitor increased the expressions of both proteins.ConclusionmiR-190a-5p can promote the polarization of BMDM from M1-type to M2-type.
Evidence from numerous animal models and clinical studies in recent years has demonstrated that macrophages play an important role in the regulation of liver fibrosis regression. The safety and efficacy of utilizing autologous macrophages for the treatment of liver fibrosis have been demonstrated in patients and shows promising application prospects, but the therapeutic effects need to be improved. Cirrhotic liver undergoes a process of marked extracellular matrix degradation after partial hepatectomy surgery, and single-cell sequencing identified multiple restorative macrophage subsets that express different matrix metalloproteinases (MMPs) at high levels. Future efforts to further characterize this population of macrophages and improve their enrichment in the liver may allow macrophage therapy to be a highly effective strategy to reverse liver fibrosis.
Objective To investigate the role of alveolar macrophages ( AMs ) in airway inflammation of smoke-induced COPD rat model and its possible regulating mechanism. Methods Twelve Wistar rats were randomly divided into a COPD group and a control group. The rat model of COPD was established with smoke exposure and LPS intrathacheal instillation. Bronchoalveolar lavage fluid ( BALF)was collected for measurement of total and differential cell counts. Then AMs were isolated and identified byimmunofluorescence. Western blot was employed to analyze the cytoplasmic and nuclear NF-κB p65 expression of AMs. The concentrations of TNF-α,macrophage inflammatory protein 2 ( MIP-2) and IL-10 in cell culture supernatantwere assayed by ELISA.Results The scores of bronchitis and mean liner intercepts in the COPD group were significantly higher than those in the control group [ 4. 33 ±1. 16 vs. 1. 33 ±0. 58,P =0. 016; ( 168. 77 ±11. 35) μm vs. ( 93. 61 ±4. 16) μm, P = 0. 000) ] . The total cell count in BALF of the COPD group was significantly higher than that in the control group ( P lt; 0. 05) , and the AMs and neutrophils were predominant [ ( 72. 00 ±2. 22) % and ( 18. 29 ±8. 34) % ] . The cytoplasmic NF-κB p65 expression of AMs in the COPD group was significantly lower , while the nuclear NF-κB p65 expression was significantly higher ( P lt; 0. 05) compared with the control group. The ELISA results showed that the concentrations of TNF-αand MIP-2 in culture supernatant of AMs in the COPD group were significantly higher than those in the control group ( P lt;0. 05) , while the concentration of IL-10 was not significantly different between the two groups ( P gt;0. 05) . Conclusions COPD rat model was established successfully with smoke exposure and LPS intratracheal instillation with a profile of macrophage-based chronic inflammation and increased secretion of TNF-αand MIP-2. The mechanismis closely related to activation of NF-κB.
In the tumor microenvironment, tumor-associated macrophage, as polarized macrophages M2 phenotype, can promote tumor progression and affect the prognosis of cancer. Significant attention has been drawn towards tumor-associated macrophage in recent years. In this review, we describe the polarization state of macrophages determined by tumor microenvironment and the recruitment of tumor-associated macrophage. We also pay special attention to the interaction between tumor-associated macrophages and tumors, discuss and summarize various targeted therapy strategies for tumor-associated macrophages, aiming to provide a reference for the future development of these novel and effective anti-cancer treatments.