Intercellular adhesion molecule 1-dependent activation of interleukin 8 expression in Candida albicans-infected human gingival epithelial cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Egusa H
PROVIDER: S-EPMC538999 | biostudies-other | 2005 Jan
REPOSITORIES: biostudies-other
Similar Datasets
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:Candidiasis is a fungal infection caused by Candida species that have formed a biofilm on epithelial linings of the body. The most frequently affected areas include the vagina, oral cavity and the intestine. In severe cases, the fungi penetrate the epithelium and cause systemic infections. One approach to combat candidiasis is to prevent the adhesion of the fungal hyphae to the epithelium. Here we demonstrate that the endocannabinoid anandamide (AEA) and the endocannabinoid-like N-arachidonoyl serine (AraS) strongly prevent the adherence of C. albicans hyphae to cervical epithelial cells, while the endocannabinoid 2-arachidonoylglycerol (2-AG) has only a minor inhibitory effect. In addition, we observed that both AEA and AraS prevent the yeast-hypha transition and perturb hyphal growth. Real-time PCR analysis showed that AEA represses the expression of the HWP1 and ALS3 adhesins involved in Candida adhesion to epithelial cells and the HGC1, RAS1, EFG1 and ZAP1 regulators of hyphal morphogenesis and cell adherence. On the other hand, AEA increased the expression of NRG1, a transcriptional repressor of filamentous growth. Altogether, our data show that AEA and AraS have potential anti-fungal activities by inhibiting hyphal growth and preventing hyphal adherence to epithelial cells.
| S-EPMC7426432 | biostudies-literature
Project description:Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.
| S-EPMC3746938 | biostudies-literature
Project description:During oropharyngeal candidiasis (OPC), Candida albicans invades and damages oral epithelial cells, which respond by producing proinflammatory mediators that recruit phagocytes to foci of infection. The ephrin type-A receptor 2 (EphA2) detects β-glucan and plays a central role in stimulating epithelial cells to release proinflammatory mediators during OPC. The epidermal growth factor receptor (EGFR) also interacts with C. albicans and is known to be activated by the Als3 adhesin/invasin and the candidalysin pore-forming toxin. Here, we investigated the interactions among EphA2, EGFR, Als3 and candidalysin during OPC. We found that EGFR and EphA2 constitutively associate with each other as part of a heteromeric physical complex and are mutually dependent for C. albicans-induced activation. Als3-mediated endocytosis of a C. albicans hypha leads to the formation of an endocytic vacuole where candidalysin accumulates at high concentration. Thus, Als3 potentiates targeting of candidalysin, and both Als3 and candidalysin are required for C. albicans to cause maximal damage to oral epithelial cells, sustain activation of EphA2 and EGFR, and stimulate pro-inflammatory cytokine and chemokine secretion. In the mouse model of OPC, C. albicans-induced production of CXCL1/KC and CCL20 is dependent on the presence of candidalysin and EGFR, but independent of Als3. The production of IL-1α and IL-17A also requires candidalysin but is independent of Als3 and EGFR. The production of TNFα requires Als1, Als3, and candidalysin. Collectively, these results delineate the complex interplay among host cell receptors EphA2 and EGFR and C. albicans virulence factors Als1, Als3 and candidalysin during the induction of OPC and the resulting oral inflammatory response.
| S-EPMC7850503 | 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:Porphyromonas gulae, an animal periodontal pathogen, possess fimbriae classified into three genotypes (A-C) based on the diversity of fimA genes encoding FimA. Accumulating evidence suggests that P. gulae strains with type C fimbriae are more virulent as compared to those with other types. The ability of these organisms to adhere to and invade gingival epithelial cells has yet to be examined. P. gulae showed the greatest levels of adhesion and invasion at a multiplicity of infection of 100 for 90 min. P. gulae type C and some type B strains invaded gingival epithelial cells at significantly greater levels than the other strains, at the same level of efficiency as P. gingivalis with type II fimbriae. Adhesion and invasion of gingival epithelial cells by P. gulae were inhibited by cytochalasin D and sodium azide, indicating the requirements of actin polymerization and energy metabolism for those activities. Invasion within gingival epithelial cells was blocked by staurosporine, whereas those inhibitors showed little effects on adhesion, while nocodazole and cycloheximide had negligible effects on either adhesion or invasion. P. gulae proteases were found to be essential for adhesion and invasion of gingival epithelial cells, while its DNA and RNA, and protein synthesis were unnecessary for those activities. Additionally, α5β1 integrin antibodies significantly inhibited adhesion and invasion by P. gulae. This is the first report to characterize P. gulae adhesion and invasion of human gingival epithelial cells.
| S-EPMC6417775 | biostudies-literature
Project description:The human fungal pathogen Candida albicans shows a significant lag in growth when diluted into fresh minimal medium. This lag is abolished by the addition of conditioned medium from a high-density culture. The active component of conditioned medium is tyrosol, which is released into the medium continuously during growth. Under conditions permissive for germ-tube formation, tyrosol stimulates the formation of these filamentous protrusions. Because germ-tube formation is inhibited by farnesol, another quorum-sensing molecule, this process must be under complex positive and negative control by environmental conditions. The identification of tyrosol as an autoregulatory molecule has important implications on the dynamics of growth and morphogenesis in Candida.
| S-EPMC387371 | biostudies-literature
Project description:BackgroundCandida albicans can form biofilms on intravenous catheters; this process plays a key role in the pathogenesis of catheter infections. This study evaluated the effect of human serum (HS) on C. albicans biofilm formation and the expression of adhesion-related genes in vitro. A C. albicans laboratory strain (ATCC90028) and three clinical strains were grown for 24 h in RPMI 1640 supplemented with HS or RPMI 1640 alone (as a control). The growth of biofilm cells of four strains was monitored by a Live Cell Movie Analyzer, and by XTT reduction assay. The expression of the adhesion-related genes BCR1, ALS1, ALS3, HWP1 and ECE1 was analyzed by RT-PCR at three time points (60 min, 90 min, and 24 h).ResultsIn the adhesion phase, C. albicans cells kept a Brownian movement in RPMI medium containing HS until a large number of germ tubes were formed. In the control group, C. albicans cells quickly adhered to the bottom of the reaction plate. Compared with RPMI 1640, medium supplemented with 3-50% HS caused a significant decrease in biofilm development (all p < 0.001). However, the presence of HS had no significant inhibitory effect on the pre-adhered biofilms (all p > 0.05). Biofilm formation was also inhibited by heat-inactivated and proteinase K pre-treated HS. The presence of 50% HS did not significantly affect the planktonic growth of C. albicans (p > 0.05). At three time points, HS inhibited expression of the ALS1 and ALS3 genes and promoted expression of the HWP1 and ECE1 genes. Significant up-regulation of BCR1 was observed only at the 90-min point.ConclusionsHuman serum reduces biofilm formation by inhibiting the adhesion of C. albicans cells. This response may be associated with the down-regulation of adhesion-related genes ALS1, ALS3 and BCR1. The inhibitory serum component is protease-resistant and heat stable.
| S-EPMC4101872 | 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