BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can sign...BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.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
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
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
Inflammatory bowel disease(IBD)is a formidable disease due to its complex pathogenesis.Macrophages,as a major immune cell population in IBD,are crucial for gut homeostasis.However,it is still unveiled how macrophages ...Inflammatory bowel disease(IBD)is a formidable disease due to its complex pathogenesis.Macrophages,as a major immune cell population in IBD,are crucial for gut homeostasis.However,it is still unveiled how macrophages modulate IBD.Here,we found that LIM domain only 7(LMO7)was downregulated in pro-inflammatory macrophages,and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)through K48-mediated ubiquitination in macrophages.As an enzyme that regulates glycolysis,PFKFB3 degradation led to the glycolytic process inhibition in macrophages,which in turn inhibited macrophage activation and ultimately attenuated murine colitis.Moreover,we demonstrated that PFKFB3 was required for histone demethylase Jumonji domaincontaining protein 3(JMJD3)expression,thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27(H3K27me3).Overall,our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis.Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.展开更多
目的通过观察辛伐他汀对脑缺血-再灌注损伤大鼠巨噬细胞炎性蛋白-3α(MIP-3α)、脑源性神经营养因子(BDNF)、活化的Caspase-3的表达及神经功能评分的影响,揭示辛伐他汀在促进脑缺血-再灌注损伤大鼠神经功能恢复中的作用。方法成年雄性Wi...目的通过观察辛伐他汀对脑缺血-再灌注损伤大鼠巨噬细胞炎性蛋白-3α(MIP-3α)、脑源性神经营养因子(BDNF)、活化的Caspase-3的表达及神经功能评分的影响,揭示辛伐他汀在促进脑缺血-再灌注损伤大鼠神经功能恢复中的作用。方法成年雄性Wistar大鼠60只,随机分为3组:缺血-再灌注损伤后辛伐他汀治疗组;缺血-再灌注损伤后生理盐水对照组;假手术组。每组各20只。采用Longa线栓法制作大鼠大脑中动脉缺血-再灌注模型,缺血2h后给予再灌注。治疗组缺血-再灌注损伤1d后口服辛伐他汀1mg·kg-1·d-1;对照组口服等量生理盐水;假手术组只分离血管。各组大鼠在治疗后1、3、5、7、14d进行神经功能评分(m NSS评分),检测血清中MIP-3α和BDNF的表达以及各组大鼠脑组织中活化的Capsase-3的表达。结果 m NSS评分结果显示在给药的前3d,治疗组与对照组相比神经功能恢复没有明显差别(P>0.05)。给药后第5天至第14天,治疗组神经功能恢复明显好于对照组(P<0.05)。血清中MIP-3α的表达结果显示,治疗组与对照组在给药后第1天没有明显差异,而从治疗的第3天开始直至实验结束。结论治疗组MIP-3α的水平始终低于对照组(P<0.05)。治疗组血清中BDNF的表达,给药后的第5天开始直至结束显著高于对照组(P<0.05)。治疗组在给药第3天和第5天后,脑组织中活化的Caspase-3表达低于对照组(P<0.05),而到给药第14天时这种差异不明显。展开更多
文摘BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.
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.
基金supported by grants from the National Natural Science Foundation of China(82373875,82173821,81973329,82273934,82073858,82104186).
文摘Inflammatory bowel disease(IBD)is a formidable disease due to its complex pathogenesis.Macrophages,as a major immune cell population in IBD,are crucial for gut homeostasis.However,it is still unveiled how macrophages modulate IBD.Here,we found that LIM domain only 7(LMO7)was downregulated in pro-inflammatory macrophages,and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)through K48-mediated ubiquitination in macrophages.As an enzyme that regulates glycolysis,PFKFB3 degradation led to the glycolytic process inhibition in macrophages,which in turn inhibited macrophage activation and ultimately attenuated murine colitis.Moreover,we demonstrated that PFKFB3 was required for histone demethylase Jumonji domaincontaining protein 3(JMJD3)expression,thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27(H3K27me3).Overall,our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis.Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
文摘目的通过观察辛伐他汀对脑缺血-再灌注损伤大鼠巨噬细胞炎性蛋白-3α(MIP-3α)、脑源性神经营养因子(BDNF)、活化的Caspase-3的表达及神经功能评分的影响,揭示辛伐他汀在促进脑缺血-再灌注损伤大鼠神经功能恢复中的作用。方法成年雄性Wistar大鼠60只,随机分为3组:缺血-再灌注损伤后辛伐他汀治疗组;缺血-再灌注损伤后生理盐水对照组;假手术组。每组各20只。采用Longa线栓法制作大鼠大脑中动脉缺血-再灌注模型,缺血2h后给予再灌注。治疗组缺血-再灌注损伤1d后口服辛伐他汀1mg·kg-1·d-1;对照组口服等量生理盐水;假手术组只分离血管。各组大鼠在治疗后1、3、5、7、14d进行神经功能评分(m NSS评分),检测血清中MIP-3α和BDNF的表达以及各组大鼠脑组织中活化的Capsase-3的表达。结果 m NSS评分结果显示在给药的前3d,治疗组与对照组相比神经功能恢复没有明显差别(P>0.05)。给药后第5天至第14天,治疗组神经功能恢复明显好于对照组(P<0.05)。血清中MIP-3α的表达结果显示,治疗组与对照组在给药后第1天没有明显差异,而从治疗的第3天开始直至实验结束。结论治疗组MIP-3α的水平始终低于对照组(P<0.05)。治疗组血清中BDNF的表达,给药后的第5天开始直至结束显著高于对照组(P<0.05)。治疗组在给药第3天和第5天后,脑组织中活化的Caspase-3表达低于对照组(P<0.05),而到给药第14天时这种差异不明显。
