Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a colon cancer cell line (HT29).

ABSTRACT: BACKGROUND AND PURPOSE: We investigated the ability of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, to modulate expression of ICAM-1 and VCAM-1 in the colon cancer cell line HT29. EXPERIMENTAL APPROACH: We analysed the effect of celecoxib on ICAM-1 and VCAM-1 protein and mRNA expression in HT29 cells. Experiments were performed in the presence of mitogen-activated protein kinases (MAPK) inhibitors to evaluate the involvement of these kinases in this phenomenon. We evaluated adhesion of HT29 cells to FCS-coated plastic wells in the presence of celecoxib or MAPK inhibitors. Furthermore, we studied the effect of celecoxib on apoptosis. KEY RESULTS: Celecoxib down-regulated ICAM-1 and VCAM-1 expression in HT29 cells in a time- and dose-dependent way. Celecoxib reduced activation of p38 and p55 c-Jun terminal NH(2) kinase (JNK) MAPKs, but did not affect p46 JNK or p42/44 MAPK phosphorylation. Pretreatment with SB202190 or SP600125, specific inhibitors of p38 and JNK MAPKs, respectively, reduced ICAM-1 and VCAM-1 expression in HT29 cells dose-dependently. Adhesion of HT29 cells to FCS-coated plastic wells was inhibited dose-dependently by celecoxib, and also by SB202190 and SP600125. Celecoxib showed a pro-apoptotic effect, inducing Bax and BID but down-regulating Bcl-2. CONCLUSIONS AND IMPLICATIONS: Our findings show that celecoxib caused down-regulation of ICAM-1 and VCAM-1, affecting the adhesive properties of HT29 cells in a COX-2 independent way, inhibiting p38 and p55 MAPKs and activating a pro-apoptotic pathway.

SUBMITTER: Gallicchio M

PROVIDER: S-EPMC2267284 | biostudies-other | 2008 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression.

Project description:BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) is highly expressed during inflammation and can promote the progression of colorectal cancer. Interactions between cancer cells and vascular endothelial cells are key events in this process. Recently, the selective COX-2 inhibitor, celecoxib, was shown to inhibit expression of the adhesion molecules, ICAM-1 and VCAM-1, in the human colon cancer cell line HT29 and to inhibit adhesion of HT29 cells to FCS-coated plastic wells. Here, we evaluated the effects of celecoxib on adhesion of HT29 cells to human umbilical vein endothelial cells (HUVEC), mediated by ICAM-1 and VCAM-1, to assess further the potential protective effects of celecoxib on cancer development. EXPERIMENTAL APPROACH: Celecoxib was incubated for 4 h with HT29 cells and HUVEC and adhesion was quantified by a computerized micro-imaging system. Expression analysis of ICAM-1 and VCAM-1 cell adhesion molecules was performed by western blot. KEY RESULTS: Celecoxib (1 nM-10 microM) inhibited, with the same potency, adhesion of HT29 cells to resting HUVEC or to HUVEC stimulated by tumour necrosis factor-alpha (TNF-alpha), mimicking inflammatory conditions. Analysis of ICAM-1 and VCAM-1 expression showed that celecoxib inhibited expression of both molecules in TNF-alpha-stimulated HUVEC, but not in resting HUVEC; inhibition was concentration-dependent and maximal (about 50%) at 10 microM celecoxib. CONCLUSIONS AND IMPLICATIONS: In conclusion, our data show that celecoxib inhibits HT29 cell adhesion to HUVEC and expression of ICAM-1 and VCAM-1, in stimulated endothelial cells. These effects may contribute to the chemopreventive activity of celecoxib in the development of colorectal cancer.

| S-EPMC2275462 | biostudies-other

αB-crystallin/HspB5 regulates endothelial-leukocyte interactions by enhancing NF-κB-induced up-regulation of adhesion molecules ICAM-1, VCAM-1 and E-selectin.

Project description:αB-crystallin is a small heat shock protein, which has pro-angiogenic properties by increasing survival of endothelial cells and secretion of vascular endothelial growth factor A. Here we demonstrate an additional role of αB-crystallin in regulating vascular function, through enhancing tumor necrosis factor α (TNF-α) induced expression of endothelial adhesion molecules involved in leukocyte recruitment. Ectopic expression of αB-crystallin in endothelial cells increases the level of E-selectin expression in response to TNF-α, and enhances leukocyte-endothelial interaction in vitro. Conversely, TNF-α-induced expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin is markedly inhibited in endothelial cells isolated from αB-crystallin-deficient mice. This is associated with elevated levels of IκB in αB-crystallin deficient cells and incomplete degradation upon TNF-α stimulation. Consistent with this, endothelial adhesion molecule expression is reduced in inflamed vessels of αB-crystallin deficient mice, and leukocyte rolling velocity is increased. Our data identify αB-crystallin as a new regulator of leukocyte recruitment, by enhancing pro-inflammatory nuclear factor κ B-signaling and endothelial adhesion molecule expression during endothelial activation.

| S-EPMC3779083 | biostudies-literature

ICAM-1 clustering on endothelial cells recruits VCAM-1.

Project description:In the initial stages of transendothelial migration, leukocytes use the endothelial integrin ligands ICAM-1 and VCAM-1 for strong adhesion. Upon adhesion of the leukocyte to endothelial ICAM-1, ICAM-1 is clustered and recruited to the adhered leukocyte, promoting strong adhesion. In this study, we provide evidence for the colocalization of VCAM-1 at sites of ICAM-1 clustering. Anti-ICAM-1 antibody-coated beads were used to selectively cluster and recruit ICAM-1 on primary human endothelial cells. In time, co-localization of ICAM-1 and VCAM-1 around the adherent beads was observed. Biochemical pull-down assays showed that ICAM-1 clustering induced its association to VCAM-1, suggesting a physical link between these two adhesion molecules. The association was partly dependent on lipid rafts as well as on F-actin and promoted adhesion. These data show that VCAM-1 can be recruited, in an integrin-independent fashion, to clustered ICAM-1 which may serve to promote ICAM-1-mediated leukocyte adhesion.

| S-EPMC2840377 | biostudies-literature

Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression.

Project description:Vascular cell adhesion molecule-1 (VCAM-1) plays important roles in development and inflammation. Tumor necrosis factor-? (TNF-?) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin-matrix signaling, respectively. Integrin costimulatory signals modulate inflammatory gene expression, but the important control points between these pathways remain unresolved. We report that pharmacological FAK inhibition prevented TNF-?-induced VCAM-1 expression within heart vessel-associated endothelial cells in vivo, and genetic or pharmacological FAK inhibition blocked VCAM-1 expression during development. FAK signaling facilitated TNF-?-induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-?-induced VCAM-1 production. FAK inhibition also triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase-dependent polyubiquitination and degradation. These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover.

| S-EPMC3384409 | biostudies-literature

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM).

Project description:Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

| S-EPMC8148879 | biostudies-literature

Butyrate Decreases ICAM-1 Expression in Human Oral Squamous Cell Carcinoma Cells.

Project description:Short-chain fatty acids (SCFA) are bacterial metabolites that can be found in periodontal pockets. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) within the epithelium pocket is considered to be a key event for the selective transmigration of leucocytes towards the gingival sulcus. However, the impact of SCFA on ICAM-1 expression by oral epithelial cells remains unclear. We therefore exposed the oral squamous carcinoma cell line HSC-2, primary oral epithelial cells and human gingival fibroblasts to SCFA, namely acetate, propionate and butyrate, and stimulated with known inducers of ICAM-1 such as interleukin-1-beta (IL1β) and tumor necrosis factor-alfa (TNFα). We report here that butyrate but not acetate or propionate significantly suppressed the cytokine-induced ICAM-1 expression in HSC-2 epithelial cells and primary epithelial cells. The G-protein coupled receptor-43 (GPR43/ FFAR2) agonist but not the histone deacetylase inhibitor, trichostatin A, mimicked the butyrate effects. Butyrate also attenuated the nuclear translocation of p65 into the nucleus on HSC-2 cells. The decrease of ICAM-1 was independent of Nrf2/HO-1 signaling and phosphorylation of JNK and p38. Nevertheless, butyrate could not reverse an ongoing cytokine-induced ICAM-1 expression in HSC-2 cells. Overall, these observations suggest that butyrate can attenuate cytokine-induced ICAM-1 expression in cells with epithelial origin.

| S-EPMC7084181 | biostudies-literature

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis.

Project description:Leptospirosis is a multisystemic zoonotic disease with infiltration of visceral organs by Leptospira. The capacity of the vascular endothelium to grant immune cell recruitment and activation in target organs during the disease course remains poorly characterized. We ascertained the levels of expression of several soluble cell adhesion molecules (CAM) notably expressed by endothelial cells in human leptospirosis. We prospectively enrolled 20 hospitalized patients and compared them to 10 healthy controls. Disease severity was defined by one or more organ failures, or death. Plasmatic concentrations of soluble CAM were assessed by multiplex bead assay at the time of patient presentation (M0) and 1 month after hospital discharge. The levels of soluble E-selectin (sCD62E) and soluble intercellular adhesion molecule 1 (sICAM-1, sCD53) were significantly increased in patients compared to controls (p<0.0001) and at 1 month (p<0.0001) with median values at 978 ng/ml (interquartile ranges 787-1164; sCD62E) and 1021 ng/ml (690-1428; sCD53). At M0, Soluble P-selectin level (sCD62P) was found to be decreased with levels at 60 ng/ml (0-631) versus 711 ng/ml (343-1113) for healthy controls (p<0.05). Levels of sICAM-3 (sCD50), sVCAM-1 (vascular cell adhesion molecule, sCD106) and sPECAM-1 (platelet endothelial cell adhesion molecule, sCD31) were not different from healthy subjects at M0. This study shows that two adhesion molecules, shed as soluble forms, are elevated during the acute phase of leptospirosis: E-selectin and s-ICAM1. These molecules may interfere with the process of immune cell recruitment to clear Leptospira at tissue levels.

| S-EPMC5501535 | biostudies-literature

Cytokine-induced autophagy promotes long-term VCAM-1 but not ICAM-1 expression by degrading late-phase IκBα.

Project description:Pro-inflammatory cytokines are known to induce endothelial cell autophagy, but the role of autophagy in regulating the expression of pro-inflammatory molecules has not been characterized. We hypothesized that autophagy facilitates expression of endothelial adhesion molecules. TNFα and IL-1β induced autophagy markers in human umbilical vein endothelial cells and inhibition of autophagy by 3-methyladenine (3-MA) blocked adhesion of Jurkat lymphocytes. Interestingly, 3-MA suppressed VCAM-1 but not ICAM-1 expression at 24 hours but not 6 hours. 3-MA suppressed VCAM-1 transcription and decreased nuclear NF-κB p65 level at 6 hours but not at 2 hours. Cytokines induced a biphasic degradation of IκBα and 3-MA selectively blocked the late-phase IκBα degradation. Our results suggest that cytokine-induced autophagy contributes to late-phase IκBα degradation, facilitates NF-κB nuclear translocation and VCAM-1 transcription for long-term VCAM-1 expression. With a cytokines array assay, we found that 3-MA also inhibited IP-10 expression. These findings provide new information about the role of endothelial autophagy in persistent expression of VCAM-1 and IP-10 which enhance lymphocyte recruitment and adhesion to endothelium.

| S-EPMC5622139 | biostudies-literature

Analysis of extracellular matrix and adhesion molecules expression in ALL cell line

2010-05-01 | GSE18516 | GEO

Analysis of extracellular matrix and adhesion molecules expression in ALL cell line

Project description:The acute lymphoblastic leukemia cells lines JM-1, REH, Nalm-27, and SUP-B15 were analyzed for baseline expression of extacellular matrix and adhesion molecules using a pathway focused cDNA microarray (SABiosciences). RNA isolated from the ALL cell lines JM-1, REH, Nalm-27, and SUP-B15 was analyzed using the Extracellular Matrix and Adhesion Molecules Oligo GEArray (SABIosciences).

2010-05-01 | E-GEOD-18516 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data