Expression of macrophage inflammatory protein-1αin Kupffer cells following liver ischemia or reperfusion injury in rats

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.

Macrophage Inflammatory Protein-1 Beta (MIP-1<i>β</i>) and Platelet Indices as Predictors of Spontaneous Bacterial Peritonitis<br>—MIP, MPV and PDW in SBP

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.

Expression of Macrophage Inflammatory Protein 1α in the Endothelial Cells Exposed to Diamide

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.

Tuftsin衍生物TP影响肿瘤相关巨噬细胞MIP-1α分子表达

目的探讨TP对肿瘤相关的趋化因子巨噬细胞炎性蛋白1-α(MIP-1α)表达的影响。方法使用RT-PCR的试验方法,检测小鼠巨噬细胞Ana-1细胞和肿瘤组织中提取的巨噬细胞中MIP-1α的表达;建立小鼠S180肉瘤细胞皮下移植瘤双瘤模型,待肿瘤体积生长至约250 mm3时,将其中一侧建立术后残瘤模型,并开始以8 mg·kg-1剂量的TP给药,隔天1次,给药4次后,分离肿瘤组织,免疫组化检测MIP-1α的表达。结果不同浓度TP对小鼠TAMs的MIP-1α表达较空白对照组明显减少,并呈剂量依赖性;体内试验中,TP处理组的荷瘤小鼠的肿瘤组织MIP-1α与对照组相比表达明显降低,接近于阳性药环磷酰胺组;但是MIP-1α在小鼠Ana-1细胞和TAMs中的mRNA表达量差异没有统计学意义;不同浓度TP对小鼠Ana-1细胞的MIP-1α表达差异也没有统计学意义。结论 TP不能影响小鼠Ana-1细胞系的MIP-1α表达,但TP对肿瘤组织中的巨噬细胞MIP-1α的表达有明显影响;MIP-1α有可能是TP抗癌作用机制的新靶点。

Effect of pharmacological intervention on MIP-1α,MIP-1β and MCP-1 expression in patients with psoriasis vulgaris

Objective:To detect the expression level of macrophage inflammatory protein-1(MIP-1)α,MIP-1βand monocyte chemoattractant protein-1(MCP-1)in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.Methods:The level of MIP-1α,MIP-1βand MCP-1 in peripheral blood from 50 patients with psoriasis vulgaris and 50 normal controls were measured by enzyme linked immunosorbent assay.The correlation with psoriasis area and severity index(PASI)was analyzed.The level of MIP-1α,MIP-1βand MCP-1 was compared between psoriasis vulgaris patients at active stage and resting stage.And the change in MIP-1α,MIP-1βand MCP-1 before and after therapy was also observed.Results:The content of MIP-1α,MIP-1βand MCP-1 in patients with psoriasis vulgaris was(1342.78±210.30),(175.28±28.18)and(266.86±32.75)ng/L,respectively,significantly higher than those in control group(P<0.05).The expression level of MIP-1α,MIP-1βand MCP-1 in peripheral blood of patients with psoriasis vulgaris was positively correlated wilh PASI(P<0.01).After acitretin therapy,expression level of MIP-1α,MIP-1βand MCP-1 in peripheral blood of patients with psoriasis vulgaris was significantly decreased.Conclusions:Chemokine factor MIP-1α,MIP-1βand MCP-1 may be involved in the pathogenesis of psoriasis vulgaris.

Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer therapy.By re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)cancers.However,these therapies can also induce autoimmune-like side effects in healthy tissue across the body.One of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI malignancies.We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

Effect of glucocorticoid on MIP-1α and NF-кb expressing in the lung of rats undergoing mechanical ventilation with a high tidal volume

BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α （MIP-1α） in plasma and bronchoalveolar lavage fluid （BALF） and the expression of MIP-1α mRNA and nuclear factor-kappa B （NF-кB） p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.METHODS： Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury （VILI） group, a dexamethasone （DEX） group and a budesonide （BUD） group. The content of MIP-1a in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-кBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.RESULTS： The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the DEX and BUD groups were signifi cantly lower than those in the VILI group （P〈0.001）. Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no signifi cant differences between them （P〉0.05）.CONCLUSIONS： Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-кB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.

The clinical significance of dynamic changes of MIP-1α, MIP-1βand MCP-1 levels in patients with acute pancreatitis

Objective:To observe dynamic changes of MIP-1α, MIP-1β and MCP-1 in Acute pancreatitis patients, and to evaluate the value of MIP-1α, MIP-1β and MCP-1 in acute pancreatitis severity assessment.Methods: A total of 112 cases of acute pancreatitis were divided into mild pancreatitis (MAP group, 44 cases), moderate severe acute pancreatitis group (MSAP group, 36 cases) and severe acute pancreatitis group (SAP group, 32 cases). Serum MIP-1α, MIP-1βand MCP-1 levels were detected by enzyme-linked immunosorbent assay in patients at 1st, 4th day, 7th days.Results:(1) In 1st day, Serum concentrations of MIP-1α, MIP-1β and MCP-1 were significantly increased in three Groups, There were significant differences between the control group, MAP, MSAP and SAP group. (2) Serum concentrations of MIP-1α, MIP-1β and MCP-1 reached the peak level on 4th day in MAP group and were significantly higher than the level of those on 1st day. In the MSAP and SAP group, serum concentration of MIP-1α, MIP-1β and MCP-1 reached the peak level on 1st day, and significantly higher than the level of those on the 4th day and 7th day. There was a significant difference between MSAP group and MAP group, SAP group and MSAP group in the serum concentration of MIP-1α, MIP-1β and MCP-1 at each monitoring time.Conclusions:MIP-1α, MIP-1β and MCP-1 levels have the rule of dynamic change in Patients with acute pancreatitis, which are useful in evaluating the severity of the patients with acute pancreatitis.

Predictors of Spontaneous Bacterial Peritonitis (SBP) in Liver Cirrhosis: Current Knowledge and Future Frontiers

Spontaneous bacterial peritonitis (SBP) in patients with cirrhotic liver disease is a serious complication that contributes to the high morbidity and mortality rate seen in this population. Currently, there is a lack of consensus amongst the research community on the clinical predictors of SBP as well as the risks and benefits of prophylactic antibiotic therapy in these patients. Pharmacological gastric acid suppression (namely with PPIs and H2RAs) are frequently prescribed for these patients, many times without a clear indication, and may contribute to gut bacterial overflow and SBP development. However, this remains controversial as there are conflicting findings in SBP prevalence between PPI/H2RA-users and non-users. In addition, studies show recent antibiotic use, whether for SBP prophylaxis or for another infectious process, appear to be associated with higher rates of SBP and drug-resistant organisms. Other researchers have also explored the link between zinc, platelet indices (MPV), and macrophage inflammatory protein-1 β (MIP-1β) levels in liver cirrhosis, all of which appear to be promising markers for classifying SBP risk and diagnosis. This literature review was limited by the number and quality of studies available as most are retrospective in nature. Thus, more ongoing, prospective studies and trials are needed to judge the true value of the findings in the studies reviewed in hopes that they can guide appropriate prevention, diagnosis, and management of SBP.

美罗培南联合去甲万古霉素治疗重度肺部感染患者疗效评价

目的探讨美罗培南联合去甲万古霉素治疗重度肺部感染患者的疗效以及对呼吸指标、血清巨噬细胞炎症蛋白-1α(MIP-1α)、可溶性髓系细胞触发受体-1(s TREM-1)水平及预后的影响。方法选取2016年4月至2016年11月在我院住院治疗的重度肺部感染患者82例作为研究对象,采用随机数字表法分为观察组和对照组,每组41例。对照组患者给予美罗培南治疗,观察组在对照组治疗的基础上联合去甲万古霉素治疗,比较两组患者的治疗效果以及呼吸指标、血清炎症因子水平的变化情况。结果治疗2周后,观察组患者的治疗总有效率(97.56%)明显高于对照组(80.49%),临床疗效优于对照组,差异有统计学意义(P<0.05);观察组患者的Pa CO2显著低于对照组,Pa O2显著高于对照组,差异有统计学意义(P<0.01);观察组患者的MIP-lα、s TREM-1、降钙素原(PCT)水平均明显低于对照组,脂联素(APN)水平显著高于对照组,差异有统计学意义(P<0.01)。结论美罗培南联合去甲万古霉素治疗重度肺部感染患者疗效确切,有利于改善患者的呼吸功能及炎症反应状态,促进患者康复,值得推广应用。

巨噬细胞炎性蛋白-1与1型糖尿病

巨噬细胞炎性蛋白-1（MIP-1）是一种趋化因子，与受体结合后，可以发挥趋化和促进炎症的生物学作用，能引起多种炎症性疾病。研究表明，MIP-1α可以导致破坏性胰岛炎以及自发性1型糖尿病，而MIP-1β则对1型糖尿病起保护性作用。本文对MIP-1的结构、功能及其在1型糖尿病中的作用机制进行综述。

Effects of Wenxiao Ⅱ Decoction on the expression of MCP-1 and VCAM-1 in atherosclerotic rabbits

OBJECTIVE:To observe the effects of different doses of Wenxiao Ⅱ Decoction on the expression of monocyte chemoattractant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1) in an experimental model of atherosclerosis in rabbits and to explore the mechanism by which it alleviates atherosclerosis.METHODS:Sixty 3-4 month-old New Zealand rabbits of both sexes were randomly divided into six groups:simvastain;model;blank;and high-dose,mid-dose,and low-dose Wenxiao Ⅱ Decoction groups.Except for those in the blank group,all rabbits were fed a high-cholesterol diet.Carotid atherosclerosis was established by balloon-induced injury to the endothelium of the carotid artery in conjunction with consumption of a high-cholesterol diet.After 8 weeks,all rabbits were killed to evaluate the expression of MCP-1 and VCAM-1 by immunohistochemical staining.RESULTS:Expressions of MCP-1 and VCAM-1 were significantly decreased in all groups except the blank group compared with the model group(P<0.05).When compared with the simvastain group only variation of MCP-1 expression in low-dose group was not appreciable,and the differences were indistinct(P<0.05).When comparing among Wenxiao Ⅱ Decoction groups,MCP-1 expression in the mid-and high-dose groups was significantly lower than that seen in the low-dose group(P<0.01),but there were no differences among three dosage groups with respect to VCAM-1 expression(P>0.05).CONCLUSION:These data suggested that high,mid,and low doses of Wenxiao Ⅱ Decoction can inhibit the expression of MCP-1 and VCAM-1,which may prevent the formation of or stabilize atherosclerotic plaques.There may be a direct relationship between the dosage of Wenxiao Ⅱ Decoction and its therapeutic efficacy.

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis

OBJECTIVE: To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. METHODS: Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. RESULTS: Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. CONCLUSIONS: The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.