The genetic polymorphisms of intercellular cell adhesion molecules and breast cancer susceptibility: a meta-analysis

Intercellular cell adhesion molecules (ICAMs) genetic polymorphisms have been considered to be implicated in the development of breast cancer. However, the previous reports are conflicting. Therefore, we performed a meta-analysis to assess the association between three polymorphisms, including ICAM1 K469E, ICAM5 V301I, ICAM5 rs281439, and breast cancer risk. The meta-analyses are based on a literature search of PubMed, CNKI and VIP database up until August 2011. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using review manager 5.0.25 package. In total, five populations (2,020 cases and 2,012 controls) on ICAM1 K469E polymorphism, four populations (1,797 cases and 2,244 controls) on ICAM5 V301I polymorphism and five populations (2,744 cases and 3,006 controls) on ICAM5 rs281439 variant were included. Overall, the meta-analysis showed no significant association between ICAM1 K469E polymorphism and breast cancer risk. However, a significant association was observed for ICAM5 V301I polymorphism (VV vs. II: OR = 1.48, 95 % CI 1.04–2.13, P = 0.03; VV/VI vs. II: OR = 1.25, 95 % CI 1.05–1.48, P = 0.01). In addition, there was a significant association between ICAM5 rs281439 variant and breast cancer risk (GG vs. CC: OR = 1.31, 95 % CI 1.03–1.65, P = 0.03). Our meta-analysis suggests that the ICAM5 V301I and rs281439 variants but not ICAM1 K469E polymorphism may contribute to the susceptibility of breast cancer. Given the limited sample sizes, further investigation is needed.     

Intercellular adhesion molecule-1 gene K469E polymorphism and ischemic stroke: a case-control study in a Chinese population

Background Intercellular adhesion molecule-1 (ICAM-1) was involved in the pathogenetic mechanisms responsible for ischemic stroke (IS). Population-based sample have revealed gene-gender interaction in blood pressure which is major risk for IS. We sought to evaluate whether ICAM-1 K469E polymorphism was involved in the causation of IS and whether it was different between female and male. Methods A 1:1 case-control study was conducted. The K469E polymorphism of ICAM-1 gene were analyzed by polymerase chain reaction (PCR) and restriction enzyme analysis in Chinese patients with IS (n = 309) and elderly subjects without IS (n = 309). Results ICAM-1 K469E polymorphism was significantly associated with IS. Interestingly, a further analysis stratified by sex found that there was significance between 469E genotypes and IS in female, but not in male. Multiple regression analysis revealed that ICAM-1 K469E polymorphism was still significantly associated with IS, compared with ICAM-1 KK genotype in all population (OR = 1.60, P = 0.030). Stratified by sex, EE combined EK was contributory factor to IS in female (OR = 3.03, P = 0.004), but not in male. After adjustment for confounding factors, the interaction between female and ICAM-1 EK/EE genotypes was found (OR = 3.54, P = 0.001). Conclusions It is suggested that the ICAM-1 469E allele may be important in the pathogenesis of ischemic stroke, especially in female but not in male. Xiao-Xia Li and Jian-Ping Liu have contributed equally.     

Intercellular adhesion molecule 1 gene K469E polymorphism is associated with coronary heart disease risk: a meta-analysis involving 12 studies

Coronary atherosclerosis is a leading cause of coronary heart disease (CHD). Atherosclerotic lesion is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The ICAM1 gene-E469K polymorphism has been reported to be associated with CHD, but results were conflicting. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, and CNKI databases were searched for case–control studies published up to August 2011. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twelve eligible studies, comprising 2,157 cases and 1,952 controls, were included in the meta-analysis. The pooled result showed that the ICAM1 gene-E469K polymorphism was significantly associated with an increased risk of CHD (OR = 1.496, 95% CI = 1.363–1.642, for the allele K vs. allele E; OR = 1.919, 95% CI = 11.635–2.253, for the K allele carriers vs. EE). Subgroup analysis supported the results in the Asian populations and in the Caucasian populations. This meta-analysis suggests that the ICAM1 gene K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD among Asian and Caucasians populations.     

ICAM-1K469E 位点A 等位基因可降低EV71 手足口病发生率

目的:研究ICAM-1基因K469E位点、MCP-1A2518G位点基因多态性及sICAM-1、MCP-1在血清中表达水平与EV71手足口病的关系,探讨EV71型手足口病的遗传易感因素。方法:运用限制性片段长度多态性-聚合酶链反应(PCR-RFLP)检测急性期EV71感染阳性的手足口病患儿和正常儿童中ICAM-1K469E位点及MCP-1A2518G位点碱基变异情况,同时采用双夹心抗体法(ELISA)检测血清sICAM-l和MCP-1水平。结果:EV71手足口病组患儿血清中sICAM-l和MCP-1水平均显著高于正常对照组(P均<0.01)。EV71手足口病组ICAM-1K469E位点中,A等位基因的频率显著低于对照组(x2=6.897,P<0.01)。EV71手足口病组患儿MCP-1基因型分布、等位基因频率与对照组比较均无统计学意义(P>0.05)。结论:sICAM-1表达水平和其基因K469E位点多态性与EV71手足口病有关,A等位基因可降低EV71手足口病发生率。MCP-1表达水平与EV71手足口病感染有关,但MCP-1A-2518G位点基因多态性与EV71手足口病感染无关。     

ICAM gene cluster SNPs and prostate cancer risk in African Americans

Intercellular adhesion molecules (ICAMs) are known to be involved in various human cancers. An ICAM gene cluster lying within a 26 kb region on chromosome 19p13.2, and containing ICAM1, ICAM4, and ICAM5 has recently been identified as harboring a breast and prostate cancer susceptibility locus in two populations of European ancestry from Germany and Australia. The objective of this study was to confirm the ICAM association with prostate cancer in a sample of African American prostate cancer cases (N = 286) and controls (N = 391). Six single nucleotide polymorphisms (SNPs) within the three ICAM genes were genotyped. To control for potential population stratification an ancestry-adjusted association analysis was performed. We found that ICAM1 SNPs, −9A/C (rs5490) and K469E (rs5498) were associated with prostate cancer risk in men with a family history of prostate cancer (P = 0.008). Specifically, increased risk was observed for individuals who possessed the CC genotype of the −9 A/C variant (odds ratio = 2.5; 95% CI = 1.0–6.3) and at least one G allele of non-synonymous K469E variant (odds ratio = 1.8; 95% CI = 1.2–3.1). Strong linkage disequilibrium was observed across the ICAM region (P < 0.001). A common haplotype within the ICAM gene cluster, harboring the −9A/C variant was significantly associated with prostate cancer (P = 0.03), mainly due to men with family history (P = 0.01). Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer.     

中国汉族人群ENPP1基因K121Q多态与2型糖尿病的关联及Meta分析

多个欧洲白人的Meta分析表明核苷酸焦磷酸酶1(Ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1)基因K121Q多态与2型糖尿病相关联, 但在日本人、韩国人和中国台湾人的研究中没有发现相关性, 而在中国大陆人群中二者的关联研究结果不尽一致。文章调查了湖北地区539例2型糖尿病患者和404名正常人ENPP1基因K121Q多态性。基因型及等位基因频率在病例组和对照组间没有显著差异(P＞0.05), 但经性别、年龄和体重指数调整后的Logistic回归分析揭示XQ基因型与2型糖尿病显著相关(OR=1.5, 95%CI: 1.39~1.62, P<0.001)。对性别进行的亚组分析显示, 女性病例组Q等位基因和XQ基因型的频率显著高于对照组(Q: 12.4% vs. 6.1%, P=0.001; XQ: 23.7% vs. 11.7%, P=0.001)。结果表明ENPP1基因K121Q多态与湖北汉族人2型糖尿病的关联存在性别差异, 在女性中更明显。文章是对中国大陆人群进行的第一个Meta分析, 结果显示Q等位基因增加2型糖尿病的发病风险(OR=1.42, P=0.042)。     

Intracellular Adhesion Molecule-1 K469E Gene Polymorphism and Risk of Diabetic Microvascular Complications: A Meta-Analysis

Background

A number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting.

Methods

A comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model.

Results

Seven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04–1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13–2.81, P = 0.01; OR = 1.10, 95% CI 0.79–1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02–1.55, P = 0.04).

Conclusions

This meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.     

ICAM‐1 and MKL‐1 polymorphisms impose considerable impacts on coronary heart disease occurrence

This study was aimed to explore the correlation of intercellular adhesion molecule‐1 (ICAM‐1) K469E and megakaryoblastic leukaemia factor‐1 (MKL‐1) ?184C/T polymorphisms with the susceptibility to coronary heart disease (CHD) in the Chinese Han population. 100 CHD patients and 91 healthy people that had no blood connection with each other were enrolled in this case‐control study. ICAM‐1 and MKL‐1 polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) approach. Multiple logistic regression was used to analyse the correlation between polymorphisms of ICAM‐1 and MKL‐1 and CHD susceptibility. Differences of genotype and allele frequencies of the two SNPs between case and control groups were analysed by chi‐square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were indicated relative susceptibility of CHD. The distributions of ICAM‐1 and MKL‐1 polymorphisms in each group conformed to Hardy‐Weinberg equilibrium (HWE). After adjusting for traditional risk factors, the TT genotype frequency of MKL‐1 ?184C/T polymorphism was found significantly higher in case group than in control group (P < .05). Meanwhile, T allele frequency increased in case group compared with control group, and the differences had statistical significance (P = .04, OR = 2.34, 95% CI = 1.34‐5.26). Logistic regression analysis in this study proved that smoking, hypertension, diabetes and triglyceride (TG) were all risk factors for CHD ICAM‐1 K469E polymorphism has no association with the onset of CHD. But MKL‐1 ?184C/T polymorphism is associated with the risk of CHD and T allele might be a susceptibility factor for CHD.     

Single-nucleotide polymorphism g.1548G > A (E469K) in human ICAM-1 gene affects mRNA splicing pattern and TPA-induced apoptosis

The single-nucleotide polymorphism (SNP) g.1548G > A (E469K) in the human intercellular adhesion molecule-1 (ICAM-1) gene has been suggested to have an association with several types of inflammatory diseases. The polymorphism is located at the three-base position upstream of the splice donor site that produces an alternatively spliced short isoform (ICAM-1-S). To clarify its functional relevance, we studied RNA splicing patterns by comparing cells with different genotype (G/G cells and A/A cells). G/G cells expressed a lower amount of ICAM-1-S mRNA than A/A cells. Since ICAM-1-S has no transmembrane or intracellular domain, ICAM-1 signal transduction and cell-cell contact including Fas-FasL interaction may be influenced. In addition, we studied the effect of this change on FLIP-L mRNA and apoptosis. FLIP-L mRNA tended to decrease, while cell death induced by phorbol 12-myristate 13-acetate was increased. These results suggest that the g.1548 polymorphism modifies inflammatory immune responses by changing cell-cell interaction and then regulating apoptosis.     

Role of ICAM-1 polymorphisms (G241R,K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells

Atherosclerosis (As) is characterized by chronic inflammation and is a major cause of human mortality. ICAM-1-mediated adhesion of leukocytes in vessel walls plays an important role in the pathogenesis of atherosclerosis. Two single nucleotide polymorphisms (SNPs) of human intercellular adhesion molecule-1 (ICAM-1), G241R and K469E, are associated with a number of inflammatory diseases. SNP induced changes in ICAM-1 function rely not only on the expression level but also on the single-molecule binding ability which may be affected by single molecule conformation variations such as protein splicing and folding. Previous studies have shown associations between G241R/K469E polymorphisms and ICAM-1 gene expression. Nevertheless, few studies have been done that focus on the single-molecule forces of the above SNPs and their ligands.     

Analysis of <Emphasis Type="Italic">ICAM1</Emphasis> gene polymorphism in Slovak multiple sclerosis patients

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.     

Further evidence for the role of ENPP1 in obesity: association with morbid obesity in Finns

The aim of this study was to investigate a series of single-nucleotide polymorphisms (SNPs) in the genes MC2R, MC3R, MC4R, MC5R, POMC, and ENPP1 for association with obesity. Twenty-five SNPs (2-7 SNPs/gene) were genotyped in 246 Finns with extreme obesity (BMI > or = 40 kg/m2) and in 481 lean subjects (BMI 20-25 kg/m2). Of the obese subjects, 23% had concomitant type 2 diabetes. SNPs and SNP haplotypes were tested for association with obesity and type 2 diabetes. Allele frequencies differed between obese and lean subjects for two SNPs in the ENPP1 gene, rs1800949 (P = 0.006) and rs943003 (P = 0.0009). These SNPs are part of a haplotype (rs1800949 C-rs943003 A), which was observed more frequently in lean subjects compared to obese subjects (P = 0.0007). Weaker associations were detected between the SNPs rs1541276 in the MC5R, rs1926065 in the MC3R genes and obesity (P = 0.04 and P = 0.03, respectively), and between SNPs rs2236700 in the MC5R, rs2118404 in the POMC, rs943003 in the ENPP1 genes and type 2 diabetes (P = 0.03, P = 0.02 and P = 0.02, respectively); these associations did not, however, remain significant after correction for multiple testing. In conclusion, a previously unexplored ENPP1 haplotype composed of SNPs rs1800949 and rs943003 showed suggestive evidence for association with adult-onset morbid obesity in Finns. In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes.     

Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 × 10(-9)), PNPLA3 (rs738409, P = 5.8 × 10(-9)), RELA (rs1049728, P = 2.7 × 10(-16)), and SH2B3 (rs3184504, P = 2.9 × 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.     

CYP27B1 polymorphisms variants are associated with type 1 diabetes mellitus in Germans

CYP27B1 (25-hydroxyvitamin D(3)-1alpha-hydroxylase) catalyzes the metabolization of 25-hydroxyvitamin D(3) to 1,25(OH)(2)D(3) the most active natural Vitamin D metabolite. 1,25(OH)(2)D(3) plays a role in the regulation of autoimmunity and cell proliferation and prevents the development of autoimmune diabetes mellitus in animal models besides other autoimmune disorders. One hundred and eighty-seven families with one offspring affected with type1diabetes mellitus were genotyped for the polymorphisms in the promoter region (-1260 C/A) and intron 6 (2338 T/C) of the CYP27B1 gene on chromosome 12 q13.1-13.3 and extended transmission disequilibrium tests (ETDT) were performed. The haplotype CT (-1260 A/2338 T) was significantly more often transmitted to affected offspring (96 transmitted (T) versus 63 not transmitted (NT), P = 0.0089). While the AT (-1260 C/2838 T) was significantly less often transmitted (37 T versus 60 NT, P = 0.0195). This study suggests that CYP27B1 haplotypes may confer susceptibility to type 1 diabetes mellitus in Germans.     

Linkage disequilibrium testing of four interleukin-1 gene-cluster polymorphisms in Danish multiplex families with insulin-dependent diabetes mellitus

The molecules of the interleukin 1 (IL-1) system have been suggested to play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), and polymorphisms in the genes encoding IL-1beta (IL1B), the IL-1 Type 1 receptor (IL1RTI) and the IL-1 receptor antagonist (IL1RN) molecules have been associated with IDDM in case-control studies. It can be difficult to exclude selection biases in case-control studies leading to spurious association. This risk is eliminated when using the transmission disequilibrium test (TDT). Hence, by means of the TDT we have investigated four intragenic IL-1 gene-cluster polymorphisms, the IL1B AvaI, the IL1B TaqI, the IL1RTI PstI and the IL1RN 2(nd)intron polymorphisms, for linkage and intra-familial association with IDDM in Danish IDDM multiplex family material comprising 245 families. We found no evidence for overall linkage or intra-familial association between any of the polymorphisms and IDDM. In addition, we did not find linkage between any of the polymorphisms and IDDM in HLA-DR3/4 heterozygous or HLA-non-DR3/4 heterozygous IDDM subjects, respectively. In conclusion, by means of intra-familial TDT analysis we found no linkage or intra-familial association between IDDM and the four IL-1 gene-cluster polymorphisms in Danish IDDM multiplex family material.     

Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus

Vitamin D has important immuno-modulatory properties and it influences insulin secretion. It acts through a vitamin D receptor (VDR), for which several gene polymorphisms have been described. The Uruguayan population presents several epidemiological characteristics that make it different from that of other counties, including other Latin-American countries. It went through miscegenation processes, with a tri-hybrid European, Amerindian and African origin, with no contribution from isolated Amerindian communities. Such differences have important consequences for the relationship between frequencies of several genes in the general population and their association with the diabetes mellitus. We examined the prevalence of VDR gene polymorphisms in the general population and their relation to type 1 diabetes in a parent-case design. One hundred unrelated individuals from the general population and 45 parent-patient triads with a child affected with type 1 diabetes were genotyped for FokI, BsmI and TaqI VDR gene polymorphisms by RFLP-PCR. We used a transmission disequilibrium test to assess preferential transmission of parents to affected offspring. The prevalence of the three VDR polymorphisms was: allele F = 48%, B = 35%, T = 64%. The f, b, T alleles and heterozygous genotypes were found at a high frequency in this population. Among 36 informative heterozygous parental genotypes, 30 transmitted the F allele (probability of transmission = 83%). The other two polymorphisms did not show significant transmission. We suggest that FokI polymorphism indicates susceptibility to type 1 diabetes mellitus in the Uruguayan population.     

The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians.

The K121Q polymorphism of the human plasma cell membrane glycoprotein 1 (PC-1) gene is known to be associated with diabetes mellitus type 2 in some populations studied, with contradictory results. The purpose of the present study was to examine a possible association between the presence of diabetes and the PC-1 K121Q polymorphism in a German Caucasian population. Associations between the polymorphism and various metabolic and anthropometric parameters were also examined. The presence of the K121Q variant was investigated using polymerase chain reaction restriction fragment-length polymorphism in 402 subjects with diabetes (231 men, 171 women, age 63+/-11 yrs, body mass index 28.7+/-5.1 kg/m2) and in 432 age- and sex-matched controls (247 men, 185 women, age 64+/-7 yrs, BMI 26.5+/-3.7 kg/m2). Ninety-seven subjects were carriers of the K121Q polymorphism in the control and 110 in the diabetic group (allelic frequency 11.9% and 14.7%, respectively, P=0.25). The polymorphism had no significant influence on the presence of atherosclerotic disease, body mass index, and blood pressure, both, in diabetics and in non-diabetic controls. Our data suggest that the K121Q polymorphism of the PC-1 gene is not associated with diabetes, obesity, hypertension or atherosclerosis in a German Caucasian population.     

Inhibition of Molt-4-endothelial adherence by synthetic peptides from the sequence of ICAM-1.

Previous studies have shown that inflammatory pathologies are mediated by lymphocyte adhesion to endothelium and subsequent transmigration through the endothelial monolayer. Lymphocyte-endothelial adherence is, in part, caused by the leukocyte integrin LFA-1 binding to ICAM-1, its ligand on endothelial cells. Synthetic peptides based on specific amino acid sequences of human ICAM-1 inhibit the adherence of a lymphocytic cell line, Molt-4, to cytokine-stimulated endothelial cells. A total of 26 peptides spanning the extracellular domains of ICAM-1 were evaluated for their inhibitory activity in two cell adhesion assays. Binding of fluorescently labeled Molt-4 cells to TNF-stimulated human umbilical vein endothelial cells was inhibited reproducibly by peptides ICAM1-20, ICAM26-50, ICAM40-64, ICAM132-146, and ICAM345-375. Three overlapping sequences of the peptide ICAM40-64, KELLLPGNNRKVYELSNVQEDSQPM, were synthesized and tested as well, and the sequence KELLLPGNNRKV showed the greatest inhibition. The inhibitory activity of these peptides was confirmed using a second assay, inhibition of aggregation of the Epstein-Barr virus-transformed B-lymphoblast line JY. Polyclonal antibodies were developed in rabbits by immunization with two of the peptides and characterized for their ability to inhibit lymphocyte-endothelial adherence. These studies predict potential sites for interaction of the integrin receptor, LFA-1, with its ligand, ICAM-1. Thus lymphocyte-endothelial interaction, and resulting inflammation, may be partially mediated by the association of ICAM-1 with LFA-1 at the specific molecular locations identified in this study.     

Influence of polyelectrolyte multilayer films on the ICAM-1 expression of endothelial cells

Recently, the use of polyelectrolyte films has been suggested as a new versatile technique of surface modification aimed at tissue engineering. In the present study, we evaluated the expression of intercellular adhesion molecule (ICAM)-1 of endothelial cells (ECs) seeded on two types of polyelectrolyte multilayer films either terminated by poly(D-lysine) (PDL) or poly(allylamine hydrochloride) (PAH). This work showed that chemical stimulations with tumor necrosis factor (TNF)-alpha induced the ICAM-1 expression of ECs differently depending largely on the film architecture employed. Compared with PAH-ending films, the PDL-ending ones upregulated the ICAM-1 expression of the ECs after a prolonged exposition to TNF-alpha, rendering this film type less favorable in tissue engineering. Cytochalasin D (an F-actin disrupting agent) showed the involvement of the cytoskeleton in the upregulation of ICAM-1 for cells deposited on films terminated by PDL. The PAH-ending films did not perturb the ICAM-1 expression of ECs and might thus enhance the seeding of ECs in vascular engineering.