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Results for “Cell Adhesion Molecules”

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PubMed2003

Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients.

OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.

Aged↗

PubMed2003

Methotrexate inhibits proliferation and regulation of the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cultured human umbilical vein endothelial cells.

BACKGROUND: The mechanism by which a low dose of methotrexate (MTX) works to treat psoriasis is not clear. The overexpression of cell adhesion molecules on dermal vessels is important in the pathogenesis of psoriasis and is probably induced by upregulation of tumour necrosis factor (TNF)-alpha. OBJECTIVES: To determine the effects of MTX at concentrations comparable with in vivo levels after the administration of low-dose MTX to human umbilical vein endothelial cells (HUVEC) on the growth and expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). METHODS: Cell proliferation assay, immunostaining, immunoblotting, cell enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed to examine the effects of MTX on HUVEC. RESULTS: MTX inhibited the proliferation of HUVEC at 10-7 mol L-1 and 10-6 mol L-1 without showing cytotoxic effects. It also inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expression by HUVEC at 10-6 mol L-1. The inhibitory effect of MTX was more pronounced on ICAM-1 expression than on VCAM-1 expression. RT-PCR analysis revealed that TNF-alpha-induced ICAM-1 gene expression was strongly downregulated by MTX. CONCLUSIONS: Low-dose MTX may act on psoriasis by suppressing the TNF-alpha-induced expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Inhibition of neovascularization may be another mechanism of action of MTX.

Blotting, Western↗

PubMedDate not supplied

Effect of divalent cations on the affinity and selectivity of alpha4 integrins towards the integrin ligands vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1: Ca2+ activation of integrin alpha4beta1 confers a distinct ligand specificity.

A microtiter plate assay measuring the binding of cells expressing integrins alpha4beta1 or alpha4beta7 to VCAM-1 and MAdCAM-1, expressed as Ig fusion proteins, was used to explore the interplay between the variables of integrin beta-chain, identity and density of ligand, and identity and concentration of activating cations. Both Mn2+ and Mg2+ supported binding of either integrin to either ligand. Ca2+ supported only the binding of alpha4beta1 to VCAM-Ig. Cation concentrations required for half-maximal binding (EC50) ranged from 0.8-280 microM for Mn2+ and 0.8-30 mM for Mg2+, being thus 2-3 logs lower for Mn2+ compared to Mg2+ independent of ligand. EC50 values for binding of alpha4beta1 to VCAM-Ig were 30-45-fold lower compared to MAdCAM-Ig, while alpha4beta7 showed an opposite 3-15-fold selectivity for MAdCAM-Ig over VCAM-Ig. The density of ligand required for adhesion via alpha4beta1 was markedly lower with Mn2+ versus Mg2+, and with VCAM-Ig versus MAdCAM-Ig. These results were interpreted in terms of a coupled equilibrium model, in which binding of activating metal ions and of integrin ligands each stabilizes activated integrin. We conclude that Mn2+ and Mg2+ bind to common regulatory sites with different affinities, producing similar activated states of the integrin. The resulting activated alpha4beta1 binds more strongly to VCAM-Ig versus MAdCAM-Ig by 30-45-fold, while similarly activated alpha4beta7 binds more strongly to MAdCAM-Ig versus VCAM-Ig by 3-15-fold. Inhibition studies showed that Ca2+ also binds to regulatory sites on both integrins. However, the Ca2+-activated state of alpha4beta1 is distinct from that achieved by Mn2+ and Mg2+, possessing increased selectivity for binding to VCAM-1 versus MAdCAM-1.

Antibodies, Monoclonal↗

PubMed2003

RIFLE: a novel ring zinc finger-leucine-rich repeat containing protein, regulates select cell adhesion molecules in PC12 cells.

Cell adhesion molecules play a critical role in cell contacts, whether cell-cell or cell-matrix, and are regulated by multiple signaling pathways. In this report, we identify a novel ring zinc finger-leucine-rich repeat containing protein (RIFLE) and show that RIFLE, expressed in PC12 cells, enhances the Serine (Ser)21/9 phosphorylation of glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) resulting in the inhibition of GSK-3 kinase activity and increase of beta-catenin levels. RIFLE expression also is associated with elevated E-cadherin protein levels but not N-cadherin. The regulation of these cell adhesion-associated molecules by RIFLE is accompanied by a significant increase in cell-cell and cell-matrix adhesion. Moreover, increase in cell-cell adhesion but not cell-matrix adhesion by RIFLE can be mimicked by selective inhibition of GSK-3. Our results suggest that RIFLE represents a novel signaling protein that mediates components of the Wnt/wingless signaling pathway and cell adhesion in PC12 cells.

Amino Acid Sequence↗

PubMed1993

Preparative mini-slab gel continuous elution electrophoresis: application for the separation of two isoforms of rat hepatocyte cell adhesion molecule, cell-CAM 105, and its associated proteins.

A simple method for performing continuous elution electrophoresis using a mini-slab-gel system has been developed. The high resolving power of this method provides a means to separate complex mixtures of proteins and recover individual peptides in high yields. Recoveries between 89 and 99% were achieved using a single percentage gel to separate a mixture of standard proteins radiolabeled with 125I. Peptide fragments between 2.5 and 60 kDa generated by CNBr digestion of albumin were isolated within 150 min. Application of continuous elution electrophoresis to the purification of proteins associated with the rat hepatocyte cell adhesion molecule, cell-CAM 105, resulted in complete separation of the two predominant isoforms and the purification of three immunologically unrelated proteins that were coisolated during immunoaffinity chromatography.

Adenosine Triphosphatases↗

PubMed1987

The origin of the immune system. The possibility that immunoglobulin superfamily molecules and cell adhesion molecules of chicken and slime mould are all related.

It has been suggested that the neural cell adhesion molecules (N-CAM) are members of the Ig superfamily. We have examined structural homology between the N-CAM and other superfamily molecules in detail. The Ig-like domains of N-CAM have overall sizes similar to those of Ig constant domains or major histocompatibility complex (MHC) domains. Significant sequence homology was found between the N-CAM Ig-like domains and several other Ig superfamily members, such as T4, T8, IgA transport receptor, Ig VH, Ig C mu 4, and others. A comparison of the second domain of T4 (255 amino acids) with the central domain of N-CAM (302 amino acids) has demonstrated a significant sequence homology. Furthermore, a cell adhesion protein, cs-A, of slime mould, Dictyostelium, also seems to be related to N-CAM. It appears that the Ig superfamily of the immune system originated from more ubiquitous cell recognition molecules which are common in all metazoan species.

Amino Acid Sequence↗

PubMed2004

Homing-associated cell adhesion molecules and cell cycle status on the nucleated cells in the bone marrow, mobilized peripheral blood and cord blood.

Homing-associated cell adhesion molecules (H-CAM) on the CD34+ cells play an important role for the engraftment process following hematopoietic stem cell transplantation (HSCT). However, it seems that not only CD34+ cells but also other nucleated cells (NCs) with H-CAM could be implicated in the engraftment process and the proliferation of hematopoietic stem cells. We investigated the differences of HCAM and cell cycle status on the NCs in cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PB). The proportions of CXCR4+ cells within the NC populations were greater in CB than in PB or BM (p=0.0493), although the proportions of CXCR4+, CD44+, and CD49d+ cells within the CB CD34+ cell populations were same within BM or PB. A lower proportion of CD34+CD49d+ cells within the CD34+ cell populations was more noted in CB than in PB or BM (p=0.0085). There were no differences in cell cycle status between CB and BM or PB. Our results suggest that the migrating potential of CB would be enhanced with increased CXCR4 expression on the NCs, but the adhesion potential of CB CD34+ cells would be less than that of PB and BM. These findings may help explain why the lower cell dose is required and engraftment is delayed in cord blood stem cell transplantation.

Antigens, CD34↗

PubMed1990

Integrins and other cell adhesion molecules.

Cell-cell and cell-substratum interactions are mediated through several different families of receptors. In addition to targeting cell adhesion to specific extracellular matrix proteins and ligands on adjacent cells, these receptors influence many diverse processes including cellular growth, differentiation, junction formation, and polarity. Several families of adhesion receptors have been identified. These include: 1) the integrins, heterodimeric molecules that function both as cell-substratum and cell-cell adhesion receptors; 2) the adhesion molecules of the immunoglobulin superfamily, which are involved in cell-cell adhesion and especially important during embryo-genesis, wound healing, and the inflammatory response; 3) the cadherins, developmentally regulated, calcium-dependent homophilic cell-cell adhesion proteins; 4) the LEC-CAMs, cell adhesion molecules with lectin-like domains that mediate white blood cell/endothelial cell adhesion; and 5) homing receptors that target lymphocytes to specific lymphoid tissue. In this review we summarize recent data describing the structure and function of some of these cell adhesion molecules (with special emphasis on the integrin family) and discuss the possible role of these molecules in development, inflammation, wound healing, coagulation, and tumor metastasis.

Aging↗

PubMed1997

Rat mast cell lines bind to the vascular cell adhesion molecule-1 (VCAM-1) and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1).

Mast cells are key mediators of allergy and inflammation. Increased mast cell numbers are observed in the gut during helminth infestation and at many sites of inflammation. To determine whether mast cells express functional receptors for endothelial cell adhesion molecules, we studied the adhesion of two rat mucosal-type mast cell lines RBL-1 and RCMC-1 to transfected mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and VCAM-1. Both mast cell lines expressed high levels of alpha4 integrins on their surface and bound to CHO cells transfected with VCAM-1. Anti-alpha4 mAbs, TA-2 and L25, inhibited the specific adhesion of the mast cells to VCAM-1 by about 92 and 63%, respectively. Both of the mast cell lines also demonstrated an increased adhesion to CHO cells transfected with MAdCAM-1. The adhesion of RBL-1 to MAdCAM-1 was also significantly inhibited by the anti-alpha4 mAbs TA-2, L25, and HP2/1 by 39, 76, and 42%, respectively. In addition, RBL-1 cells adhered to both VCAM-1 and MAdCAM-1 under both static and nonstatic (shear) conditions, and this was also inhibited by the anti-alpha4 mAb TA-2. Thus, mucosal-type mast cell lines express functional alpha4 integrins that can mediate adhesion to VCAM-1 and MAdCAM-1. These results suggest a mechanism for mast cell accumulation at sites of inflammation and in the gut.

Animals↗

PubMed1998

MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule).

From a differential mRNA display comparing a non- and a highly metastasizing human melanoma cell line, we isolated and characterized memD. memD is preferentially expressed in the highly metastasizing melanoma cell lines of a larger panel. The encoded protein, MEMD, is identical to activated leukocyte cell adhesion molecule (ALCAM), a recently identified ligand of CD6. ALCAM is involved in homophylic (ALCAM-ALCAM) and heterophylic (ALCAM-CD6) cell adhesion interactions. We have studied MEMD/ALCAM cell-cell interactions between human melanoma cells. The expression of this cell adhesion molecule not only correlates with enhanced metastatic properties and with aggregational behavior of human melanoma cells as tested by FACS analysis, but transfection experiments also make clear that MEMD/ALCAM expression is essential for cell-cell interaction of the investigated human melanoma cells. As the melanoma cell lines analyzed are all CD6 negative, these results strongly suggest that MEMD/ALCAM is an adhesion molecule mediating homophylic clustering of melanoma cells. MEMD/ALCAM expression is not restricted to subsets of leukocytes and melanoma cells, it can also be found in healthy organs and in several other malignant tumor cell lines. Besides, MEMD/ALCAM is also expressed in cultured endothelial cells, pericytes and melanocytes, in xenografts derived from the radial and vertical growth phase and in 4 of 13 melanoma metastasis lesions. The potential role is discussed of MEMD/ALCAM mediated cell-cell interactions in migration of mobile cells (ie, activated leukocytes, metastasizing tumor cells) through tissues.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2000

Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis: findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1.

OBJECTIVE: To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. METHODS: We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. RESULTS: Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. CONCLUSION: NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.

Aged↗

PubMed1993

Effect of dexamethasone, 6-mercaptopurine and cyclosporine A on intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression.

The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is increased in immune-mediated diseases. These adhesion molecules promote the adherence of inflammatory cells to parenchymal target cells. We have examined the effect of immunosuppressants on the expression of ICAM-1 and VCAM-1 in a renal tubular epithelial cell line. We found that dexamethasone (4-40 micrograms/mL), the azathioprine metabolite 6-mercaptopurine (10-100 micrograms/mL) and cyclosporine A (0.1-1 microgram/mL) have no effect on the basal and the tumor necrosis factor-alpha- or interleukin-1-stimulated expression of these adhesion molecules. We conclude that these immunosuppressants do not directly influence the expression of ICAM-1 and VCAM-1 by renal tubular epithelium.

Animals↗

PubMed1995

Circulating selectins, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in hyperthyroidism.

Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.

Adult↗

PubMed1989

[A highly sialylated, embryonic form of the neural cell adhesion molecule in Wilms tumor: identification of a cell adhesion molecule as a onco-developmental antigen].

The neural cell adhesion molecule NCAM is a general Ca2+ -independent cell adhesion molecule which exerts important functions during the development of the nervous system. NCAM polypeptides exist in various isoforms all of which have a similar extracellular domain structure containing a homophilic binding site for establishment of cell-cell contacts. A common structural feature of NCAM is the presence of homopolymers of alpha 2,8-linked sialic acid residues, the so-called polysialic acid, which is developmentally regulated. It undergoes a change from a highly less sialylated short chain form from embryonic to adult life. The polysialic acid regulates the homophilic adhesive properties of NCAM. The highly sialylated form of NCAM typically found in developing tissues decreases homophilic NCAM-NCAM interactions and, therefore, cell-cell contacts due to its large excluded volume and electric repulsive forces. We have used a monoclonal antibody against polysialic acid, polyclonal antibodies against NCAM, polysialic acid specific bacteriophage-encoded endoneuraminidases and a NCAM cDNA to investigate this molecule by light and electron microscopic immunolabeling, in situ hybridization and immunochemistry. The highly sialylated form of NCAM was found to be expressed in a developmentally-regulated fashion in embryonic kidney, undetectable in the normal adult kidney and re-expressed in Wilms tumor. In Wilms tumor the blastemal cell masses as well as epithelial differentiations such as tubules and glomeruloid bodies were immunolabeled whereas the stroma did not label for polysialic acid. Combination of immunoprecipitation and immunoblotting using antibodies against polysialic acid and NCAM, respectively, directly demonstrated structural relationship of renal polysialic acid with NCAM polypeptide. By immunoblot analysis two NCAM isoforms of approximately 120 and 140 kD were found in Wilms tumor. Immuno-electron microscopy provided direct morphological evidence for prevention of cell-cell contacts due to the presence of a thick cell surface coat composed of polysialic acid. In nephroblastomatosis complexes only blastemal cells exhibited immunocytochemically detectable polysialic acid. All other investigated kidney tumors, i.e. clear cell sarcoma, malignant rhabdoid tumor, cystic nephroma and renal cell carcinoma, were negative. These data allow the conclusion that the highly sialyated, embryonic form of NCAM is an onco-developmental antigen in human kidney. At the same time this is the first observation that a molecule with a well defined role for controlled cell migration and differentiation during embryonic organ development represents an onco-developmental antigen.

Cell Adhesion Molecules, Neuronal↗

PubMed1994

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and in malignant epithelial tumors.

Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin (Ig) superfamily, was tested and measured on tissue sections from 16 undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors of various origin. Neoplastic cells of all cases of U-NPC were diffusely and intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA) and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two tumors. In the other epithelial tumors focal or diffuse staining for ICAM-1 was observed in 40 cases (66%), whereas reactivity for VCAM-1 was detected in a single case of metastatic undifferentiated carcinoma of unknown origin. The biopsy specimens of U-NPC showed variable infiltration by leukocytes, which were positive for the integrins lymphocyte function antigen-1 (LFA-1) and alpha-4/beta-1, the corresponding ligands for ICAM-1 and VCAM-1. The possibility that ICAM-1 and VCAM-1 on neoplastic cells may favor the intratumoral recruitment of leukocytes in a way similar to that occurring in crypt epithelium of the palatine tonsil is discussed.

Adolescent↗

PubMed2001

Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues.

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.

Adult↗

PubMed2002

Lack of stimulatory effect of dienogest on the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by endothelial cell as compared with other synthetic progestins.

OBJECTIVES: Monocyte adhesion to endothelial cells is an important initial event at the onset of atherosclerosis. It is partially mediated by the expression of adhesion molecules on the endothelial cell surface. While estrogens inhibit the development of atherosclerosis, the effect of co-administered progestin remains controversial. We examined the effect of progestins on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. METHODS: In HUVECs, mRNA expression of progesterone receptors (PRs) and androgen receptors (AR) was determined by RT-PCR. HUVECs were stimulated by interleukin-1beta (IL-1beta) for 24 h with or without various steroids, and then the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was semiquantified by ELISA. RESULTS: In all preparations of HUVECs used in this study, RT-PCR confirmed mRNA expression of both isoforms of PR, PR-A and PR-B, as well as AR. Addition of progesterone (10(-10)-10(-7) M) or dienogest (DNG) (10(-10)-10(-8) M) did not affect IL-1beta-stimulated ICAM-1 or VCAM-1 expression. In contrast, medroxyprogesterone acetate, norethindrone acetate and levonorgestrel (10(-10)-10(-8) M) dose-dependently increased cell adhesion molecules. The progestin-induced increase was blocked by the concomitant addition of mifepristone, a PR antagonist, but not by hydroxyflutamide, an AR antagonist, indicating that the progestin stimulation was mediated predominantly via PR. CONCLUSIONS: These results suggest that DNG, unlike other synthetic progestins, lacks stimulation of cell adhesion molecules. For the prevention of atherosclerosis, estrogen in combination with DNG may be a suitable regimen in hormone replacement therapy in postmenopausal women.

Arteriosclerosis↗

PubMed2006

In vivo low-density lipoprotein exposure induces intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 correlated with activator protein-1 expression.

OBJECTIVE: We tested the hypothesis that direct native low-density lipoprotein (LDL) injection into LDL receptor-deficient (LDLR(-/-)) mice would induce the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in their aortic endothelial cells, and that transcriptional regulation of this pathway involved activator protein-1 (AP-1) but not nuclear factor kappaB (NF-kappaB). METHODS AND RESULTS: Using tail vein injection of LDL into LDLR(-/-) mice, we were able to maintain atherogenic LDL blood levels, which induced ICAM-1 and VCAM-1 expression in their aortic endothelial cells after 24 hours. We were able to visualize and quantify this expression using immunohistochemistry and confocal microscopy. Under conditions in which ICAM-1 and VCAM-1 were expressed, the regulatory AP-1 proteins c-Fos and c-Jun were also highly expressed in the endothelial cell cytoplasm and observed within the cell nucleus. The NF-kappaB protein P65, although expressed in the endothelial cell cytoplasm after LDL injection, was not observed within the cell nucleus. CONCLUSIONS: Elevated LDL blood levels, maintained in vivo, increased the expression of the adhesion molecules ICAM-1 and VCAM-1 in aortic endothelial cells. This effect appeared to correlate with AP-1 but not NF-kappaB.

Animals↗