Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway / 中草药·英文版

OBJECTIVE@#Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs.@*METHODS@#MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis.@*RESULTS@#The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.@*CONCLUSION@#Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Assessment of circulating MCP-1 level and 2518A>G gene polymorphism in systemic lupus erythematosus / Avaliação do nível de MCP-1 circulante e polimorfismo do gene 2518A> G no lúpus eritematoso sistêmico

Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE). This study aims to investigate the possible role of a functional polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene and MCP-1 blood level in the diagnosis of LN and in correlating the MCP-1 blood levels with disease activity. The study included 56 SLE patients and 56 controls. All the SLE patients suffered from LN. An analysis of MCP-1 gene polymorphism by polymerase chain reaction was performed followed by restriction fragment length polymorphism (PCR-RFLP) analysis and MCP-1 blood level was determined using the ELISA technique. Calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was performed. Serologic tests included the determination of antinuclear antibody (ANA) and anti-double-stranded (ds) DNA antibodies, Complement C3 and C4 levels. A significant increase in the frequency of genotype A/G and a decrease in the frequency of genotype A/A were found among patients with active LN compared to inactive LN. There was a statistically significant difference in the blood level of MCP-1 between LN patients and controls. Also, MCP-1 blood levels were significantly higher in active LN patients than inactive LN. A significant positive linear correlation was detected between MCP-1 blood level and SLEDAI, creatinine, and 24 hours protein in LN patients. These results suggest that an A/G genotype together with the measurement of the blood level of MCP-1 can be a useful tool for detection and follow up of active LN.

A nefrite do lúpus (LN) é um dos principais contribuintes para a morbidade e mortalidade em pacientes com o Lúpus Eritematoso Sistémico (LES). Este estudo tem como objetivo investigar o possível papel de um polimorfismo funcional na região reguladora do gene da proteína quimioatraente de monócitos-1 (MCP-1) e do nível sanguíneo de MCP-1 no diagnóstico de LN e na correlação do sangue de MCP-1 níveis com atividade da doença. O estudo incluiu 56 pacientes com LES e 56 controles. Todos os pacientes com LES sofriam de LN. Uma análise do polimorfismo do gene MCP-1 por reação em cadeia da polimerase foi realizada seguida pela análise do polimorfismo do comprimento do fragmento de restrição (PCR-RFLP) e o nível sanguíneo do MCP-1 foi determinado pela técnica ELISA. O cálculo do índice de atividade da doença sistêmica do lúpus eritematoso (SLEDAI) foi realizado. Os testes sorológicos incluíram a determinação de anticorpos antinucleares (ANA) e anticorpos anti-DNA de fita dupla (ds), níveis de Complemento C3 e C4. Um aumento significativo na frequência do genótipo A/G e uma diminuição na frequência do genótipo A/A foram encontrados entre os pacientes com LN ativo em comparação com o LN inativo. Houve uma diferença estatisticamente significante no nível sanguíneo de MCP-1 entre pacientes com LN e controles. Além disso, os níveis sanguíneos de MCP-1 foram significativamente mais altos em pacientes com LN ativo do que com LN inativo. Uma correlação linear positiva significativa foi detectada entre o nível sanguíneo de MCP-1 e SLEDAI, creatinina e proteína de 24 horas em pacientes com LN. Esses resultados sugerem que um genótipo A/G, juntamente com a medição do nível sanguíneo de MCP-1, pode ser uma ferramenta útil para a detecção e acompanhamento do LN ativo

Comparasion on Effect of Xuefu Zhuyutang and Modified Erchentang on Nonalcoholic Fatty Liver in Mice / 中国实验方剂学杂志

Objective:To compare the effect and mechanisms of modified Erchentang and Xuefu Zhuyutang on high-fat diet-induced apolipoprotein-E knockout (ApoE-/-) mice nonalcoholic fatty liver disease (NAFLD). Method:Ten C57/BL6J mice were taken as normal control group and fed with normal feed. Totally 30 ApoE-/- mice were fed with high-fat diet to establish a disease model for 4 weeks. After 4 weeks, the 30 ApoE-/- mice were divided into model group, Xuefu Zhuyutang group (hereinafter referred to as Huoxue group) and modified Erchentang group (hereinafter referred to as Huatan group) by random number table method, with 10 in each group. The normal group and the model group were intragastrically administered with normal saline. The drug-administered group was intragastrically administered at a dosage that was ten times of the adult dose, once a day, for 8 weeks. Serum and liver were collected after the end of the 12-week experiment. The serum lipid and liver function levels of each group were measured, and the liver pathological morphology was observed. Protein and mRNA expressions of liver inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic factor-1 (MCP-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The results of serum lipids and liver function showed that compared with the normal group, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the model group were significantly increased, while serum high-density lipoprotein (HDL) was significantly reduced (P<0.01). Compared with the model group, serum TG ，LDL and ALT were significantly decreased, HDL was significantly increased in the Huoxue group (P<0.05). The serum levels of TC, TG， LDL, AST and ALT in the Huatan group were significantly decreased，HDL was significantly increased (P<0.05，P<0.01), and TG was decreased. The mice serum HDL in the Huatan group was higher than that in the Huoxue group. The serum ALT in the Huoxue group was lower than that in the Huatan group. The pathological observation showed that compared with the normal group, hepatocytes in the model group had severe steatosis with many lipid droplet vacuoles, suggesting that the mouse NAFLD model was successful. Compared with the model group, each administration group alleviated hepatocyte steatosis, with no significant difference between the two administration groups. Western blot and Real-time PCR results showed that compared with the normal group, protein and mRNA expression levels of TNF-α, IL-1β, MCP-1, and MMP-9 in the model group were significantly increased (P<0.05，P<0.01). Compared with the model group, the Huoxue group significantly down-regulated the expressions of IL-1β, MCP-1 protein and MCP-1 mRNA(P<0.05，P<0.01). The Huatan group significantly reduced the expressions of IL-1β, TNF-α, MMP-9, MCP-1 protein, TNF-α and MMP-9 mRNA(P<0.05，P<0.01). Conclusion:Modified Erchentang and Xuefu Zhuyutang can alleviate the therapeutic effect of NAFLD mice to a certain extent, modified Erchentang has a better therapeutic effect.

Uric Acid Induces Inflammation, Hepatocyte Apoptosis and Deterioration of Liver Function

@#Introduction: Uric acid is a common cause of liver tissue damage due to its hepatotoxic effect. This study is aimed to investigate: (1) the effect of uric acid on liver damage which can be seen from the serum levels of SGOT and SGPT, (2) the inflammatory response demonstrated by TLR-4 and MCP-1 mRNA expression, and (3) the proportion of hepatocytes apoptosis in mice. Methods: A total of 25 adult male Swiss-Webster mice were divided into five groups: one control group and four uric acid groups (AU7, AU14, AU21 and AU28). The uric acid groups were administered with 125 mg/kgBW uric acid for 7, 14, 21, and 28 days. Following the treatment, mice were terminated and the liver was harvested. Blood sample was taken from retro-orbital vein to assess serum uric acid, SGOT, and SGPT levels. RT-PCR was performed to examine the mRNA expressions of TLR-4 and MCP-1. TUNEL staining was used to assess the proportion of apoptotic hepatocytes. Results: Induction of uric acid caused hyperuricemia, increased expression of TLR-4 and MCP-1 mRNA significantly (p<0.05) which indicated an inflammatory reaction. The levels of SGOT and SGPT were elevated significantly (p<0.05), as well as the number of hepatocyte apoptosis (p<0.05). Conclusion: Hyperuricemia affected the inflammatory response by increasing the mRNA expression of TLR-4 and MCP-1. An increased number of apoptotic hepatocytes was likely caused by the ongoing inflammatory reaction during the induction of uric acid.

Effects of inflammatory pain on inflammatory reaction and expressions of TNF-α and MCP-1 in peripheral tissue of mice / 西安交通大学学报(医学版)

Objective: To investigate the effects of inflammatory pain on local tissue structure, inflammatory reaction and expression levels of TNF-α and MCP-1 in formaldehyde-induced inflammatory pain in mice. Methods: Sixty-four adult male mice were randomly divided into NS group (40 μL of saline injected into the wrist of right forelimb), FCOH group (50 mL/L formaldehyde of 40 μL injected into the wrist of right forelimb), L group (5 μg/mL lidocaine of 0.3 mL for brachial plexus anesthesia) and FCOH+L group. Some of the tissue samples were collected at 48 h after formaldehyde modeling to observe the infiltration of inflammatory cells by HE staining. The rest were used to assess the expression levels of TNF-α and MCP-1 by Western blot. Results: Compared with NS group, FCOH group showed peak inflammatory response at 24 h (thickness of injection sites: 1.73 mm vs. 4.02 mm, temperature: 37 ℃ vs. 38.3 ℃, P<0.05). However, FCOH+L group showed intense inflammatory responses at 48 h (thickness of injection sites: 1.68 mm vs. 5.10 mm, temperature: 37 ℃ vs. 38.5 ℃, P<0.05). Furthermore, after 48 h FCOH group had a lower degree of infiltration of inflammatory cells and higher expression levels of TNF-α and MCP-1 than those in FCOH+L group (P<0.05). Conclusion: Inflammatory pain plays a significant role in the healing process of injured issues by facilitating the local inflammation and affecting the duration. The expression levels of TNF-α and MCP-1 in local tissues decrease by interrupting the transmission of pain.

Effect of Mangiferin on Morphology of Relevant Vessels and MCP-1/CCR-2 Pathway in Spontaneously Hypertensive Rats / 中国实验方剂学杂志

Objective:To observe the morphological changes of carotid artery, thoracic aorta and superior mesenteric artery in spontaneously hypertensive rats(SHR), in order to further study the effect of Mangiferin on the expressions of inflammatory factors and monocyte chemoattract protein-1 (MCP-1)/c-chemokine receptor type 2 (CCR-2) pathway in SHR. Method:Forty spontaneously hypertensive rats were randomly divided into model group, benazepril group (10 mg·kg-1·d-1) and low, medium and high-dose mangiferin groups (25, 50, 100 mg·kg-1·d-1). Eight male WKY rats of the same age were selected as normal control group. Systolic blood pressure was observed every two weeks after eight weeks of administration. Morphology of carotid artery, thoracic aorta and superior mesenteric artery was observed by hematoxylin-eosin (HE) staining. Immunohistochemical assay (IHC) and Western blot were used to detect MCP-1 and CCR-2 protein expressions in thoracic aorta. MCP-1 and CCR-2 mRNA expression levels in thoracic aorta were detected by Real-time quantitative fluorescence PCR (Real-time PCR). Result:Compared with the normal group, the inflammatory cells in the model group increased significantly, the systolic blood pressure was significantly higher than that in the WKY group (PPPPConclusion:There are inflammation damages in carotid artery, thoracic aorta and superior mesenteric artery of spontaneously hypertensive rats. Mangiferin has an anti-inflammatory effect by possibly inhibiting the expressions of MCP-1/CCR-2 pathway in SHR vessels.

Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB (NF-κB) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD). Method: Forty SD rats were randomly divided into normal group, model group, modified Erchentang group and EVP4593 (NF-κB inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling, normal and model groups were intragastrically given normal saline solution, EVP4593 group was given EVP4593(1 mg · kg-1) through subcutaneous injection, and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g · kg-1) for 14 days. The levels of high mobility group box 1(HMGB1), chemokines CXCL-2, CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB p65 (NF-κB p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4, MyD88, NF-κB p65 and p-NF-κB p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4, MyD88 and p-NF-κB p65 protein in the lung tissue. Result: The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 were increased significantly (PPκB p65 mRNA and protein were decreased significantly (PConclusion: Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-κB pathway and the reduction of the release of HMGB1, CXCL-2, CXCL-3 and MCP-1.

Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model / 中国中药杂志

This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.

Association between MCP-1 -2518A>G polymorphism and asthma susceptibility: a meta-analysis

The published data on the association between MCP-1 -2518A>G polymorphism and asthma susceptibility are inconclusive. Therefore, we performed a meta-analysis to estimate the impact of MCP-1 -2518A>G polymorphism on asthma susceptibility. PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were used to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the estimates of overall effect, and funnel plots and Egger's test were used to assess publication bias. Eight publications with 1562 asthma patients and 1574 controls were finally identified. Overall, we found no significant association between MCP-1 -2518A>G polymorphism and asthma susceptibility in any of the genetic model comparisons. After stratified analysis by ethnicity, the results showed that a significant association with asthma risk was found in Caucasians in all the genetic models. However, a protective association was found in Africans under the dominant model. The present meta-analysis suggested that the MCP-1 -2518 A>G polymorphism is a risk factor for asthma in the Caucasian population, nevertheless it has a protective effect in the African population.

Short-term insulin intensive therapy decreases MCP-1 and NF-κB expression of peripheral blood monocyte and the serum MCP-1 concentration in newlydiagnosed type 2 diabetics

ABSTRACT Objective To observe the effect of short-term insulin intensive treatment on the monocyte chemoattractant protein-1 (MCP-1) as well as on the nuclear factor-kappa B (NF-κB) expression of peripheral blood monocyte. This is also in addition to observing the serum MCP-1 level in newlydiagnosed type 2 diabetic patients and probing its anti-inflammation effects. Subjects and methods Twenty newly-diagnosed type 2 diabetic patients were treated with an insulin intensive treatment for 2 weeks. MCP-1 and NF-κB expression on the monocyte surface were measured with flow cytometry, the serum MCP-1 level was measured by enzyme linked immunosorbent assay (ELISA) during pretreatment and post-treatment. Results After 2 weeks of the treatment, MCP-1 and NF-κB protein expression of peripheral blood monocyte and serum MCP-1 levels decreased significantly compared with those of pre-treatment, which were (0.50 ± 0.18)% vs (0.89 ± 0.26)% (12.22 ± 2.80)% vs (15.53 ± 2.49)% and (44.53 ± 3.97) pg/mL vs (49.53 ± 3.47) pg/mL, respectively (P < 0.01). The MCP-1 expression on monocyte surface had a significant positive relationship with serum MCP-1 levels (r = 0.47, P < 0.01). Conclusions Short-term insulin intensive therapy plays a role in alleviating the increased inflammation reaction in type 2 diabetics.

A possible association between the -2518 A>G MCP-1 polymorphism and insulin resistance in school children

ABSTRACT Objective Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the pathophysiology of insulin resistance (IR); therefore, variants in the MCP-1 gene may contribute to the development of this disease. The aim of this study was to analyze the relationship of the -2518 A>G MCP-1 (rs1024611) gene polymorphism with insulin resistance in Mexican children. Subjects and methods A cross-sectional study was performed in 174 children, including 117 children without insulin resistance and 57 children with IR, with an age range of 6-11 years. Levels for serum insulin and high-sensitivity C-reactive protein were determined. The -2518 A>G MCP-1 polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Insulin resistance was defined as a HOMA-IR in the upper 75th percentile, which was ≥ 2.4 for all children. Results Genotype frequencies of the rs1024611 polymorphism for the insulin-sensitive group were 17% AA, 48% AG and 35% GG, and the frequency of G allele was 59%, whereas frequencies for the insulin-resistant group were 12% AA, 37% AG and 51% GG, and the frequency of G allele was 69%. The genotype and allele frequencies between groups did not show significant differences. However, the GG genotype was the most frequent in children with IR. The GG genotype was associated with insulin resistance (OR = 2.2, P = 0.03) in a genetic model. Conclusion The -2518 A>G MCP-1 gene polymorphism may be related to the development of insulin resistance in Mexican children.

Effect of Qi Kwai Granule particles on expression of TGF-β1 and MCP-1 in kidney of diabetic nephropathy rats / 中国药理学与毒理学杂志

OBJECTIVE To observe the effect of Qi Kwai Granule particles on the expression of in-terleukin 6 (IL-6), monocyte chemotactic protein 1(MCP-1) and transforming growth factor-β1(TGF-β1) in diabetic nephropathy(DN)rats and evaluate the protective effect of Qi Kwai Granule particles against renal injury of diabetic nephropathy. METHODS This experiment adopts adopted the high-sugar-high-fat diet and intraperitoneal injection of 2％ STZ+unilateral renal ligation to establish rat model of diabet-ic nephropathy.50 model rats were then randomly divided into model group,Irbesartan group,Qi Kwai Granule particles of high, medium, low dose group, 10 rats in each group. 10 normal rats were set as the sham operation group.Intragastric administration for 8 weeks were measured in rats.Measure the value of rat blood glucose by blood glucose meter,the determination of serum interleukin 6(IL-6)con-tent by ELISA, the expression of MCP-1 and TGF-β1by immunohistochemistry method. The value of rat blood glucose were measured by blood glucose meter.Serum interleukin 6(IL-6)were determinat-ed by ELISA.Expression of MCP-1 and TGF-β1were evaluated by immunohistochemistry method.RE-SULTS The blood glucose of Qi Kwai Granule particles of high,medium groups were decreased com-pared with those of the model group(P<0.05).The content of IL-6 of Qi Kwai Granule particles of high, medium groups were reduced(P<0.01). The content of MCP-1, TGF-β1in kidney of Qi Kwai Granule particles of high, medium, low dose groups were decreased (P<0.01). CONCLUSION Qi Kwai parti-cles have protective effect on renal tissue of diabetic nephropathy rats.Its mechanism might be related to the decrease of blood glucose value and IL-6,the inhibition of the expression of MCP-1 and TGF-β1.

Effects of Moxibustion on Colonic JNK Signaling Pathway in Crohn's Disease Model Rats / 世界科学技术-中医药现代化

Objective: To explore the anti-inflammatory immune mechanism in moxibustion treatment of Crohn.s disease (CD) from the perspective of c-Jun N-terminal kinase (JNK) signaling pathway, through observing the regulatory effect ofmoxibustion on colonic JNK, c-Jun, monocyte chemoattractant protein 1 (MCP-1) and cyclooxygenase 2 (COX2) in CDmodel rats. Method: Male Sprague-Dawley rats of clean grade were randomized into a normal group, a model group, amoxibustion group and a sham moxibustion group. CD model was developed by the mixture of 2, 4, 6 Trinitro-benzene-sulfonic acid (TNBS) and ethanol via enema. Hematoxylin-eosin (HE) staining was used to observe the morphologicalchanges in rat.s colon tissues for pathological scoring; enzyme-linked immunosorbent assay (ELISA) was used to detectthe contents of MCP-1, COX2, JNK, and c-Jun in colon tissues; real-time fluorescence quantitative PCR was adopted toexamine the mRNA expressions of JNK and c-Jun in rat.s colon. Result: Compared with the normal group, the modelgroup showed more significant colonic damage and thus had a higher colonic damage score (P ＜ 0.01), manifested astopical inflammation which involved the submucosa, fissuring ulcers and granuloma; the model group also showedincreased contents of protein MCP-1 and COX2, and elevated contents of JNK protein and mRNA in colon (all P ＜ 0.05), while the change in the content of c-Jun was insignificant (all P＞ 0.05) . Compared with the model group and shammoxibustion group, the colonic damage score was lower in the moxibustion group (P ＜ 0.01, P ＜ 0.05), with improvementin colonic structure and inflammation; the contents of MCP-1 and COX2 in colon tissues declined, so did the proteincontent and mRNA expression of JNK (all P ＜ 0.05), while the change in the content of c-Jun was insignificant (all P＞0.05) . There were no significant differences between the model group and sham moxibustion group comparing all theindexes (all P＞ 0.05) . Conclusion: Moxibustion down-regulates the expressions of JNK protein and mRNA in CD rat.scolon, as well as the contents of MCP-1 and COX2 in colon tissues, which is possibly one significant mechanism formoxibustion to ease intestinal inflammation and promote the repair of colon tissues in CD.

Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune response in a New Zealand white rabbit model

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin 4,2′,4′-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their 6th lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor κB (NF-κB) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon γ (IFN-γ) were evaluated through ELISA. The effects of ISL on the phosphorylation of IκBα, IKKα/β and p65 in NF-κB signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. NF-κB signaling was inhibited, in which the phosphorylation of p65, IκBα and IKKα/β were suppressed whereas the level of IκBα were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, NF-κB, IL-4 and IL-10 in treating ST.

Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms / 神经科学通报·英文版

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2) neurons. CCL2 increased NMDA-induced currents in CCR2/VGLUT2 neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

Expression and function of MCP-1 and its receptor in wAMD model mouse / 临床与实验病理学杂志

Purpose To detect the expression and the function of MCP-1 and its receptor CCR2 in wet agerelated macular degenerative (wAMD) model mouse retina. Methods C57BL/6J mouse were enrolled into the study. Model mouse of wAMD was induced with laser. Frozen sections were prepared for histopathological tests. Immunofluorescence study for MCP-1 and CCR2 was carried out. Co-expression study for CCR2/ CDllb or CCR2/CD68 was carried out. Total protein and total mRNA from the eyes of both wAMD and wild type mouse were extracted. The expression of mRNA and protein of MCP-1 and CCR2 in the eyes were determined by reverse transcription-poly-merase chain reaction (RT-PCR) and Western blots test, respectively. Results In wild type mouse, both MCP-1 and its receptor CCR2 were not detected in the retina. However in wAMD mouse, an obvious up-regulated MCP-1 and CCR2 expression was seen in the retinal pigment epithelium (RPE) cells accompanied with the increased expression of their mRNA and protein. The co-expression study showed that CCR2 co-ex-pressed with CDllb, but not with CD68. Conclusion MCP-1 and its receptor CCR2 may play a role in the wAMD through stimulation of microglia.

Clinical significance of inflammatory factors in severe EV71 hand-foot-and-mouth disease / 中国感染控制杂志

Objective To investigate the clinical significance of 5 kinds of inflammatory factors (MCP 1,IL 1β,IL-18,HMGB1,and IL-10) in severe EV71 hand-foot-and-mouth disease (HFMD).Methods Hospitalized children who were diagnosed with severe EV71 HFMD in a hospital in March August,2014 were as HFMD group,healthy children who underwent physical examination in outpatient department of the same hospital during the sameperiod were as control group,changes in expression levels of peripheral blood MCP-1,IL-1β,IL-18,HMGB1,and IL-10 of both groups were dynamically observed,clinical data of HFMD group were collected.Results There were 102 children in HFMD group,the average age was (2.18 ± 0.91) years old,80.39％ of whom were ≤3 years old;there were 77,16,and 9 cases in HFMD group at stage 2,3,and 4 respectively at admission.77,52,21,and 88 cases went through stage 2,3,4,and 5 respectively.Expression levels of 5 kinds of inflammatory factors at stage 2,3,and 4 in HFMD group were compared respectively with control group,differences were all statistically significant(all P＜0.05);expression levels of IL-10 at stage 3 and 4 in HFMD group were not significantly different (P＞0.05).In HFMD group,the expression levels of HMGB1 of stage 2,3 progression groups were both higher than recovery group(both P＜0.05).The expression levels of 5 kinds of inflammatory factors in the death group and survival group at admission were all significantly different (all P＜0.05).Conclusion The expression levels of MCP 1,HMGB1,IL-1β,IL-10,and IL-18 are closely related to the severity of HFMD,and has certain clinical significance for the prognosis of children.HMBG1 has certain predictive value in the prognosis of HFMD.

Meta analysis on MCP-1-2518G/A gene polymorphism and susceptibility of diabetic nephropathy / 重庆医学

Objective To evaluate the relation between MCP-1-2518G/A gene polymorphism and the onset risk of diabetic nephropathy(DN) by the data of collected and publishedcase control studies and using the meta analysis method .Methods All lit-eratures on moncyte chemoattractant protein-1(MCP-1)-2518G/A gene polymorphism and the onset risk of DN included in the da-tabases of PubMed ,Web of Science ,EMbase ,Cochrane Library ,CNKI ,Wanfang and VIP until October 2016 were systametically re-trieved .Then the related data were extracted .The Stata11 .0 statistical software was used to calculate the odds ratio (OR) of syn-thetic data and 95% confidence interval (CI) ,meanwhile the heterogeneity and publication bias of the studies were evaluated .Re-sults A total of 9 studies were included involving 2767 independent samples ,the number of cases was 1096 ,the control number was 1671 .For the general population ,the relationship between MCP-1 gene-2518G/A polymorphism and the onset risk of DN was not found in 4 gene models (dominant model:OR=1 .01 ,95% CI:0 .67-1 .54 ;recessive model :OR=0 .93 ,95% CI:0 .60-1 .44 ;homo-zygous model:OR=0 .93 ,95% CI:0 .70 -1 .23 ;heterozygous model :OR=0 .89 ,95% CI:0 .61-1 .31) .The subgroup analysis re-sults showed that in India population ,MCP-1-2518G/A gene polymorphism might significantly increase the onset risk of DN (domi-nant model:OR=1 .56 ,95% CI:1 .19 -2 .06) ,but in Chinese ,Turks or South Koreans ,the MCP-1-2518G/A gene polymorphism had no relation with the onset risk of DN .Conclusion In the general population ,MCP-1-2518G/A gene polymorphism has no rela-tion with the onset risk of DN .But the MCP-1 gene-2518G/A polymorphism can increase the onset risk of DN in India population , while does not increase the onset risk of DN in Chinese population ,Korean population and Turkey population .

Effects of Ginkgo biloba tablet on MPA, CD11 b and MCP-1 levels in patients with unstable angina pectoris / 中国临床药理学与治疗学

AIM:To observe the levels of monocyte-platelet aggregates (MPA) and markers of activated monocytes in patients with unstable angina pectoris (UAP) accepting Ginkgo biloba tablet treatments,and to explore its mechanisms for cardiovascular disease treatments.METHODS:The levels of MPA,CD11b,and MCP-1 were measured in 92 unstable angina pectoris (UAP) and 42 stable angina pectoris (SAP).The UAP patients were randomly assigned into routine treatment group (control group) and combined tablet treatment group (Ginkgo biloba group).The efficacy was assessed,and the levels of MPA,CD11b,and MCP-1 were measured after 28 days of treatment,respectively.RESULTS:The levels of MPA,CD11b,and MCP-1 in UAP group were higher than those in SAP group (P＜0.001).The levels of MPA and CD11b were positively correlated with MCP-1 level (P ＜ 0.01).The total rate of effective Ginkgo biloba tablet treatment was higher than that of non-Ginkgo biloba tablet treatment (P ＜ 0.05).After 28 days of treatments,the levels of MPA,CD11b,and MCP-1 in Ginkgo biloba group were significantly lower than those in control group (P ＜ 0.001).In total effective treatment group,the levels of MPA,CD11b,and MCP-1 were significantly lower after treatment than those before treatment (P ＜ 0.001),and the decreased rates of these markers after treatment were also much higher (P ＜ 0.01).CONCLUSION:There is an obvious efficacy of Ginkgo biloba tablet on unstable angina pectoris by down-regulating the levels of MPA,CD11b and MCP-1.

Improving Effect of Traditional Chinese Medicine on Diabetic Nephropathy via Regulating MCP-1 and TNF-α / 中国药师

Diabetic nephropathy ( DN) is one of the complications of diabetes, which is closely related to the pathogenesis of in-flammation. This article summarized the relevant literatures on the correlation between MCP-1 , TNF-α and DN, and the intervention of traditional Chinese medicine with DN. In kidney tissues, oxidative stress and NF-κB-dependent signal pathways induced the increase of monocyte chemoattractant protein-1 (MCP-1) expression, which could induce macrophage accumulation, proteinuria increase, renal fibrosis and renal clearance capacity decrease, and further leading to kidney damage. The clinical and experimental trails showed tumor necrosis factorαmRNA and protein levels in serum, urine and renal tissues were closely related with DN, which could be used as a bio marker to provide clinical guidance. As the therapeutic targets,MCP-1 and TNF-αcould give a novel insight into the clinical treatment of DN. Some traditional Chinese medicines or monomer could ameliorate DN by inhibiting MCP-1 and/or TNF-α. Thus, further verifi-cation or clinical application of those traditional Chinese medicines is worth trying.