Minor allele of Intercellular adhesion molecule-1 (ICAM-1) polymorphism (rs5498 1462A>G) is associated with SARS-CoV-2 infection and related mortality.
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ABSTRACT:
SUBMITTER: Padhi S
PROVIDER: S-EPMC8244367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecently, associations between intercellular adhesion molecule-1 (ICAM-1) rs5498 polymorphism and ischemic stroke (IS) were investigated by several pilot studies, but with inconsistent results. In this study, a meta-analysis was performed to better assess the relationship between ICAM-1rs5498 polymorphism and IS.MethodsPubMed, Medline, Embase, and CNKI were searched for eligible studies. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate associations between ICAM-1 rs5498 polymorphism and IS.ResultsTotally 16 studies with 2,596 cases and 11,800 controls were analyzed. A significant association with IS was observed for rs5498 polymorphism in GG versus AA + AG (recessive model, p = 0.009, OR = 1.62, 95% CI 1.13-2.32, I2 = 76%) in overall population. Further subgroup analyses showed that rs5498 polymorphism was significantly associated with IS in Caucasians in AA versus AG + GG (dominant model, p = 0.03, OR = 0.52, 95% CI 0.29-0.95, I2 = 72%), GG versus AA + AG (recessive model, p < 0.0001, OR = 2.98, 95% CI 2.05-4.31, I2 = 19%), and A versus G (allele model, p = 0.005, OR = 0.50, 95% CI 0.31-0.81, I2 = 81%). However, no any positive findings were detected for Asians.ConclusionsOur findings indicated that rs5498 polymorphism was significantly associated with individual susceptibility to IS in Caucasians, but not in Asians.
| S-EPMC6565590 | biostudies-literature
Project description:In the present study, we included currently published evidence to comprehensively evaluate the influence of the rs5498 polymorphism within the ICAM1 (intercellular adhesion molecule 1) gene on the genetic risk of multiple sclerosis. STATA 12.0 software was utilized to carry out the heterogeneity assessment, association test, and Begg's test as well as the Egger's tests and sensitivity analyses. A total of 11 high-quality case-control studies were selected from the initially retrieved 2209 articles. The lack of high heterogeneity led to the use of a fixed-effect model in all genetic models. The results of the association test showed a reduced risk of multiple sclerosis in the allelic G vs A (Passociation = 0.036, OR = 0.91) and dominant AG+GG vs AA (Passociation = 0.042, OR = 0.85) but not in other genetic models (all Passociation > 0.05). In addition, the negative results were observed in further subgroup analyses based on ethnicity or Hardy-Weinberg equilibrium in all genetic models. Data from Begg's and Egger's tests further excluded the presence of remarkable publication bias, while sensitivity analysis data supported stable outcomes. Thus, we conclude that ICAM1 rs5498 may not be related to the risk of multiple sclerosis in Caucasian or Asian populations, which still merits further research.
| S-EPMC6294617 | biostudies-literature
Project description:Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein in the immunoglobulin superfamily expressed on the surface of multiple cell populations and upregulated by inflammatory stimuli. It mediates cellular adhesive interactions by binding to the β2 integrins macrophage antigen 1 and leukocyte function-associated antigen 1, as well as other ligands. It has important roles in the immune system, including in leukocyte adhesion to the endothelium and transendothelial migration, and at the immunological synapse formed between lymphocytes and antigen-presenting cells. ICAM-1 has also been implicated in the pathophysiology of diverse diseases from cardiovascular diseases to autoimmune disorders, certain infections, and cancer. In this review, we summarize the current understanding of the structure and regulation of the ICAM1 gene and the ICAM-1 protein. We discuss the roles of ICAM-1 in the normal immune system and a selection of diseases to highlight the breadth and often double-edged nature of its functions. Finally, we discuss current therapeutics and opportunities for advancements.
| S-EPMC10215618 | biostudies-literature
Project description:BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism has been implicated in susceptibility to coronary artery disease (CAD). Several studies investigated the association of this polymorphism with CAD in different populations but the results were contradictory. A meta-analysis was conducted to assess the association between ICAM-1 K469E polymorphism and CAD susceptibility. MATERIAL AND METHODS: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used. RESULTS: Fifteen case-control studies including 3088 cases and 3466 controls were included. Overall, a significant association between ICAM-1 K469E polymorphism and CAD was observed in the dominant model (OR=1.80; 95% CI 1.62-2.01; P<0.00001; Pheterogeneity=0.40). In subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.92; 95% CI 1.51-2.43; P<0.00001; Pheterogeneity=0.98) and among Caucasians (OR=1.64; 95% CI 1.30-2.08; P<0.0001; Pheterogeneity=0.04). In the subgroup analysis by age, a significant association was found among young patients (OR=1.46; 95% CI 1.10-1.93; P=0.008; Pheterogeneity=0.21) and old patients (OR=1.92; 95% CI 1.75-2.10; P<0.00001; Pheterogeneity=0.99). Conclusions Results of this meta-analysis suggest that ICAM-1 K469E polymorphism confers a risk factor of CAD.
| S-EPMC4271799 | biostudies-literature
Project description:The overall objective of the study was to identify mechanisms through which intercellular adhesion molecule-1 (ICAM-1) augments the adhesive and fusogenic properties of myogenic cells. Hypotheses were tested using cultured myoblasts and fibroblasts, which do not constitutively express ICAM-1, and myoblasts and fibroblasts forced to express full length ICAM-1 or a truncated form lacking the cytoplasmic domain of ICAM-1. ICAM-1 mediated myoblast adhesion and fusion were quantified using novel assays and cell mixing experiments. We report that ICAM-1 augments myoblast adhesion to myoblasts and myotubes through homophilic trans-interactions. Such adhesive interactions enhanced levels of active Rac in adherent and fusing myoblasts, as well as triggered lamellipodia, spreading, and fusion of myoblasts through the signaling function of the cytoplasmic domain of ICAM-1. Rac inhibition negated ICAM-1 mediated lamellipodia, spreading, and fusion of myoblasts. The fusogenic property of ICAM-1-ICAM-1 interactions was restricted to myogenic cells, as forced expression of ICAM-1 by fibroblasts did not augment their fusion to ICAM-1+ myoblasts/myotubes. We conclude that ICAM-1 augments myoblast adhesion and fusion through its ability to self-associate and initiate Rac-mediated remodeling of the actin cytoskeleton.
| S-EPMC5506053 | biostudies-literature
Project description:BackgroundAlthough VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) have been associated with incident heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF), the associations of VCAM-1 and ICAM-1 with sensitive measures of cardiac structure/function are unclear. The objective of this study is to evaluate associations between VCAM-1, ICAM-1, and measures of cardiac structure and function as potential pathways through which cellular adhesion molecules promote HFpEF and AF risk.Methods and resultsIn MESA (Multi-Ethnic Study of Atherosclerosis), we evaluated the associations of circulating VCAM-1 and ICAM-1 at examination 2 (2002-2004) with measures of cardiac structure/function on cardiac magnetic resonance imaging at examination 5 (2010-2011) after multivariable adjustment. Mediation analysis of left atrial (LA) strain on the association between VCAM-1 or ICAM-1 and AF or HFpEF was also performed. Overall, 2304 individuals (63±10 years; 47% men) with VCAM-1 or ICAM-1, cardiac magnetic resonance imaging, and covariate data were included in analysis. Higher VCAM-1 and ICAM-1 were associated with lower LA peak longitudinal strain and worse global circumferential left ventricular strain but were not associated with left ventricular myocardial scar or interstitial fibrosis. Lower LA peak longitudinal strain mediated 8% (95% CI, 2-30) of the relationship between VCAM-1 and HFpEF and 9% (95% CI, 2-21) of the relationship between VCAM-1 and AF.ConclusionsHigher VCAM-1 and ICAM-1 were associated with lower LA function and left ventricular systolic function but were not associated with myocardial scar or interstitial fibrosis. VCAM-1 and ICAM-1 may promote HFpEF and AF risk through impaired LA reservoir function.
| S-EPMC11009988 | biostudies-literature
Project description:We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle.
| S-EPMC4323887 | biostudies-literature
Project description:Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy.
| S-EPMC3965461 | biostudies-literature
Project description:We investigated the role of caveolae in the mechanism of increased pulmonary vascular permeability and edema formation induced by the activation of polymorphonuclear neutrophils (PMNs). We observed that the increase in lung vascular permeability induced by the activation of PMNs required caveolin-1, the caveolae scaffold protein. The permeability increase induced by PMN activation was blocked in caveolin-1 knockout mice and by suppressing caveolin-1 expression in rats. The response was also dependent on Src phosphorylation of caveolin-1 known to activate caveolae-mediated endocytosis in endothelial cells. To address the role of PMN interaction with endothelial cells, we used an intercellular adhesion molecule (ICAM)-1 blocking monoclonal antibody. Preventing the ICAM-1-mediated PMN binding to endothelial cells abrogated Src phosphorylation of caveolin-1, as well as the increase in endothelial permeability. Direct ICAM-1 activation by crosslinking recapitulated these responses, suggesting that ICAM-1 activates caveolin-1 signaling responsible for caveolae-mediated endothelial hyperpermeability. Our results provide support for the novel concept that a large component of pulmonary vascular hyperpermeability induced by activation of PMNs adherent to the vessel wall is dependent on signaling via caveolin-1 and increased caveolae-mediated transcytosis. Thus, it is important to consider the role of the transendothelial vesicular permeability pathway that contributes to edema formation in developing therapeutic interventions against PMN-mediated inflammatory diseases such as acute lung injury.
| S-EPMC2664169 | biostudies-literature
Project description:The local inflammatory environment of injured skeletal muscle contributes to the resolution of the injury by promoting the proliferation of muscle precursor cells during the initial stage of muscle regeneration. However, little is known about the extent to which the inflammatory response influences the later stages of regeneration when newly formed (regenerating myofibers) are accumulating myonuclei and undergoing hypertrophy. Our prior work indicated that the inflammatory molecule ICAM-1 facilitates regenerating myofiber hypertrophy through a process involving myonuclear positioning and/or transcription. The present study tested the hypothesis that ICAM-1 enhances global transcription within regenerating myofibers by augmenting the transcriptional activity of myonuclei positioned in linear arrays (nuclear chains). We found that transcription in regenerating myofibers was ~2-fold higher in wild type compared with ICAM-1-/- mice at 14 and 28 days post-injury. This occurred because the transcriptional activity of individual myonuclei in nuclei chains, nuclear clusters, and a peripheral location were ~2-fold higher in wild type compared with ICAM-1-/- mice during regeneration. ICAM-1's enhancement of transcription in nuclear chains appears to be an important driver of myofiber hypertrophy as it was statistically associated with an increase in myofiber size during regeneration. Taken together, our findings indicate that ICAM-1 facilitates myofiber hypertrophy after injury by enhancing myonuclear transcription.
| S-EPMC9267068 | biostudies-literature