Soluble intercellular adhesion molecule-1,D-lactate and diamine oxidase in patients with inflammatory bowel disease

AIM： To study the levels of serum soluble intercellular adhesion molecule-1 （sICAM-1）, plasma D-lactate and diamine oxidase （DAO） in patients with inflammatory bowel disease （IBD）, and the potential clinical significance. METHODS： Sixty-nine patients with IBD and 30 healthy controls were included in this study. The concentration of sICAM-1 was detected with enzyme-linked immunosorbent assay, the level of D-lactate and DAO was measured by spectroscopic analysis, and the number of white blood cells （WBC） was determined by routine procedure. RESULTS： The levels of sICAM-I, DAO, and WBC in IBD patients were significantly higher than those in the control group （P 〈 0,01）, sICAM-I in IBD patients was found to be closely related to the levels of DAO and D-lactate （212.94 ± 69.89 vs 6.35 ± 2.35, P = 0.000）, DAO 212.94 ± 69.89 vs 8.65 ± 3.54, P = 0.000） and WBC （212.94 ± 69.89 vs 7.40 ± 2.61, P = 0.000）, but no significant difference was observed between patients with ulcerative colitis and patients with Crohn＇s disease. The post-treatment levels of sICAM-I, D-lactate and WBC were significantly lower than before treatment （sICAM-I 206.57 ± 79.21 vs 146.21 ± 64.43, P = 0.000）, （D-lactate 1.46 ± 0.94 vs 0.52± 0.32, P = 0.000） and （WBC 7.24 ± 0.2.33 vs 5.21 ± 3.21, P = 0.000）. CONCLUSION： sICAM-1, D-lactate and DAO are closely related to the specific conditions of IBD, and thus could be used as a major diagnostic index.

Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

AIM:To investigate the association between single nu-cleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk,biological behavior and prognosis of gastric cancer (GC) in Chinese population.METHODS:The study group consisted of 332 GC patients and 380 healthy controls.Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing.The associa-tion of ICAM-1 K469E polymorphisms and the risk of GC were studied,and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed.RESULTS:Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios:1.36;95% confidence in-terval (CI):1.01-1.84;P=0.041].GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%,respectively;P=0.002).In addition,patients at stage Ⅳ had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%,re-spectively;P=0.046).Follow-up study showed that the overall cumulative survival rate was 23.7% in AA geno-type group and 42.9% in AG and GG genotypes group.In univariate analysis,AA genotype was correlated with the overall cumulative survival (P=0.034).But in multi-variate analysis,ICAM-1 polymorphism was not an inde-pendent prognostic factor for the overall survival (relative risk,1.145;95% CI:0.851-1.540;P=0.370).CONCLUSION:Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC,predicting disease progression,and guiding individualized treatment.

Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and prediction of severe acute pancreatitis

AIM:To determine if serum inter-cellular adhesion molecule 1(ICAM-1)is an early marker of the diagnosis and prediction of severe acute pancreatitis(SAP) within 24 h of onset of pain,and to compare the sensitivity,specificity and prognostic value of this test with those of acute physiology and chronic health evaluation(APACHE)Ⅱscore and interleukin-6(IL-6). METHODS:Patients with acute pancreatitis(AP)were divided into two groups according to the Ranson's criteria:mild acute pancreatitis(MAP)group and SAP group.Serum ICAM-1,APACHEⅡand IL-6 levels were detected in all the patients.The sensitivity,specificity and prognostic value of the ICAM-1,APACHEⅡscore and IL-6 were evaluated. RESULTS:The ICAM-1 level in 36 patients with SAP within 24 h of onset of pain was increased and was significantly higher than that in the 50 patients with MAP and the 15 healthy volunteers(P<0.01).The ICAM-1 level(25 ng/mL)was chosen as the optimum cutoff to distinguish SAP from MAP,and the sensitivity,specificity,positive predictive value,negative predictive value(NPV),positive likelihood ratio and negative likelihood ratio were 61.11%,71.42%,0.6111,0.7142, 2.1382 and 0.5445,respectively.The area under the curve demonstrated that the prognostic accuracy of ICAM-1(0.712)was similar to the APACHE-Ⅱscoring system(0.770)and superior to IL-6(0.508)in distinguishing SAP from MAP. CONCLUSION:ICAM-1 test is a simple,rapid and reliable method in clinical practice.It is an early marker of diagnosis and prediction of SAP within the first 24 h after onset of pain or on admission.As it has a relatively low NPV and does not allow it to be a stand-alone test for the diagnosis of AP,other conventional diagnostic tests are required.

孟鲁司特钠抗鼻病毒RV⁃1B感染支气管哮喘小鼠模型肺组织纤维化作用的机制研究

细胞间粘附分子⁃1(Intercellular adhesion molecule⁃1,ICAM⁃1)为介导鼻病毒(Human rhinovirus,HRV)感染支气管哮喘的受体之一,在气道反应性、肺及支气管损伤、炎症因子的调控中发挥关键作用。孟鲁司特钠可缓解气道反应性,减少肺和气管损伤,同时具有抗炎作用。孟鲁司特钠是否可下调ICAM⁃1从而预防HRV感染引起的支气管哮喘尚不清楚。本研究以BALB/c小鼠为研究对象,随机分为正常对照组、正常给药组、模型对照组和模型给药组(N=30)。模型对照组、模型给药组小鼠构建RV⁃1B感染支气管哮喘模型,模型给药组给予孟鲁司特钠干预。正常对照组、正常给药组为正常小鼠,正常给药组给与孟鲁司特钠干预。检测各组小鼠肺组织RV⁃1B拷贝数,测定肺泡灌洗液中免疫球蛋白E(Immunoglobulin E,IgE)、肿瘤坏死因子⁃α(Tumor necrosis factor⁃ɑ,TNF⁃ɑ)、白细胞介素⁃4(Interferon⁃4,IL⁃4)、白细胞介素⁃13(Interferon⁃13,IL⁃13)、半胱氨酰白三烯受体1型抗体(Cysteinyl leukotriene receptor 1 antibody,CysLT1)和γ⁃干扰素(Interferon⁃γ,IFN⁃γ)水平,观察各组小鼠肺组织病理改变,并检测肺组织ICAM⁃1 mRNA和蛋白的表达水平及嗜酸性粒细胞(Eosinophilic granulocyte,EOS)凋亡水平。结果显示,模型对照组小鼠肺泡间隔及支气管中观察到胶原纤维过度沉积,肺泡腔有红细胞渗出;与模型对照组相比,模型给药组小鼠肺组织胶原纤维沉积明显减少,肺泡腔红细胞渗出减少。模型对照组和模型给药组小鼠肺组织中HRV拷贝数呈先上升后下降的趋势,但两组各时间点的HRV拷贝数无明显差异。与模型对照组相比,模型给药组小鼠肺组织ICAM⁃1 mRNA和蛋白表达水平明显降低,EOS凋亡指数显著升高。与模型对照组相比,模型给药组肺泡灌洗液IFN⁃γ水平明显升高,而IgE、TNF⁃α、IL⁃4、IL⁃13和CysLT1水平均明显降低。因此,孟鲁司特钠可下调RV⁃1B受体靶点ICAM⁃1的表达,促进EOS凋亡、降低炎症反应,从而减轻RV⁃1B感染引起的肺组织纤维化。

CIRCULATING INTERCELLULAR ADHESION MOLECULE 1 LEVELS IN SERA OF BRONCHIAL ASTHMA

Objective The aim of the study was to determine whether bronchial asthma was associated with increased levels of soluble intercellular adhesion molecule 1(sICAM 1) in serum, which might be valuble data for the effective therapy of these patients Patients and methods The concentrations of sICAM 1 were determined in sera of healthy donors and asthmatic patients using a sensitive enzyme immunoassay Results The mean(±SD) levels of serum sICAM 1 of 26 asthmatic patients (205±72 0 μg/L)was significantly higher than that of the 30 healthy volunteers (154±63 9 μg/L,P<0 01) There was no much difference between the serum levels in 12 patients suffering from atopic asthma and the levels in 14 patients with nonatopic asthma The serum concentrations of sICAM 1 were higher during asthma attacks than that during remissions in the same patients (P<0 05) Conclusion These results suggest that sICAM 1 may play a certain role in the pathophysiology of bronchial asthma,and might be signals for successful treatment

A preliminary clinical application of sICAM-1 RIA in three kinds of thyroid disease

To examine serum levels of sICAM 1 from normal controls and patients with thyroid diseases (simple goitre, Graves’ disease or Hashimoto’s thyroiditis) with 125 Ⅰ sICAM 1 RIA established in our lab Methods Using 125 Ⅰ sICAM 1 RIA, serum sICAM 1 levels of 400 healthy individuals as the normal group and 1020 patients with simple goitre (SG), Graves’ disease (GD) or Hashimoto’s thyroiditis (HT) were examined for a comporative chinical study Results The serum level of sICAM 1 ( ±s ) in the normal group was 168 43±36 23 μg/L There was no significant difference between the normal and SG groups ( P 】0 05), whereas the serum levels of sICAM 1 in autoimmune thyroid diseases (GD or HT) were higher than those in the normal or SG groups ( P 【0 05, respectively) After GD patients received one of three medical treatments, their serum sICAM 1 levels decreased ( P 【0 05) After GD patients were treated and their thyroid function decreased to normal, their serum sICAM 1 levels were lower than those in relapsed GD patients ( P 【0 05) Conclusions sICAM 1 RIA can be used to examine autoimmune thyroid diseases Serum levels of sICAM 1 can be used as a parameter in diagnosing autoimmune thyroid disease and in evaluating the effects of therapy, drug administration or relapse in GD

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Intercellular adhesion molecule-1 （ICAM-1） plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin （PMA/Io） in human umbilical vein endothelial cells （HUVECs）. Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression （RNAi） resulted in increased expression of ICAM-1 in HUVECs in HUVECs. Knockdown of SIRT1 by RNA interference Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation （CHIP） assays. Furthermore, SIRT1 RNAi increased NF-~：B p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.

Changes of pulmonary intercellular adhesion molecule-1 and CD11b/CD18 in peripheral polymorphonuclear neutrophils and their significance at the early stage of burns

Objective: To investigate the role of intercellular adhesion molecule 1 (ICAM 1) in the accumulation of polymorphonuclear neutrophils (PMN) in the lungs at the early stage of burns. Methods: Myeloperoxidase content in lung tissues and bronchoalveolar lavage fluid (BALF) were detected. ICAM 1 and its mRNA expression in lung tissues were determined by immunohistochemical method and in situ hybridization. CD11b/CD18 expression on the peripheral PMNs was measured by flowcytometry. Results: The levels of myeloperoxidase in lung tissues and BALF after burn injury were markedly higher than those of control. Expression of ICAM 1 and its mRNA in the lung tissues and CD11b/CD18 on peripheral PMNs surface was significantly increased at 2, 6, 12, 24 h after burns. Conclusions: PMNs accumulation in the lungs is related to increased ICAM 1 expression on pulmonary microvascular endothelial cells and CD11b/CD18 expression on PMN at the early stage of burn injury.

Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion

Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley （SD） rats were randomly divided into 5 groups （n = 8）： sham, sham ＋ CORM-2, IR, IR ＋ CORM-2 and IR ＋ dimethyl sulfoxide （DMSO）. Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR＋CORM-2 group and in the sham ＋ CORM-2 group were given CORM-2 （10 μmol/kg intravenous bolus） 5 minutes before reperfusion or at the corresponding time points, while rats in the IR ＋ DMSO group was treated with the same dose of vehicle （DMSO） at the same time. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule- 1 （ICAM- 1）expression, I κBα degradation and nuclear factor （NF）-κB activity in the lungs were assessed. Results： As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF- κB activity significantly increased in the IR group, but the level of I κBα decresed （P〈0.01）. Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM- 1 expression significantly decreased in the IR＋COMR-2 group （P〈0.01）, while the level of IκBα increased. Conclusions： These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-κB pathway and the leu- kocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.

Effect of Moxibustion Therapy on the Serumal Intercellular Cell Adhesion Molecule and the Histopathology of Experimental Arthritis in Rats

Objective： To observe the effects of moxibustion therapy at Shenshu （BL 23） and Zusanli （ST 36） of rats with induced rheumatoid arthritis （RA） on the serumal intercellular cell adhesion molecule-1 （ICMA-1） and the pathological tissue, to discuss the mechanism of the warming and activating effect of moxibustion. Methods： After establishing the RA rats model, the induced rats were treated with moxibustion therapy on the acupoint Shenshu （BL 23） and Zusanli （ST 36）, followed by analyzing the pathological section of the ankle of the hind limb and testing the ICAM-1 content with ELISA. Results： The plantar circumferences of the induced rat increased significantly compared with the rats in the control group （P〈0.01）, accompanying with the increase of the synovial layer, the erosion of phlogocytes to chondrocytes and the specific increase of ICAM- 1 content. After the moxibustion therapy, the plantar circumferences decreased significantly （P〈0.01） while the synovial layer tended to reduce. In addition, there was no pathological damage of the articular cartilage and the ICAM content decreased with significant deviation （P〈0.01）, compared to the model group. Conclusion： It was concluded that moxibustion therapy could inhibit the arthrosynovitis and hyperplasia, ameliorate the erosion of phlogocyte to cartilage, prevent articular periosteal lesions and delay the pathological course. The warming and activating effect of moxibustion therapy may involve the inhibition of the formation of ICAM- 1 and pannus.