Intercellular Adhesion Molecular-1 Expression Research Articles

Atorvastatin suppresses lipopolysaccharide-induced inflammation in human coronary artery endothelial cells

The present study was designed to examine the effects of atorvastatin on vascular inflammatory responses in human coronary artery endothelial cells(HCAECs), when challenged by lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) ligand. HCAECs were pretreated with atorvastatin and induced by LPS. The expression of TLR4, interleukin -6(IL-6), monocyte chemoattractant protein 1(MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecular-1(ICAM-1), nuclear factor-κB (NF-κB) and p38 mitogen activated protein kinase(p38 MAPK) were evaluated using Real-time polymerase chain reaction, cytokine ELISA assay and Western blotting. The results showed that pretreatment with atorvastatin down-regulated the expression of TLR4 in LPS-activated HCAECs. Atorvastatin also attenuated the LPS-induced expression of interleukin IL-6 and MCP-1, at both the transcription and translation level in HCAECs. LPS-induced endothelial cell adhesion molecules, ICAM-1 and VCAM-1 expression were also reduced by pretreatment with atorvastatin. Furthermore, atorvastatin efficiently suppressed LPS-induced phosphorylation of NF-κB and p38 MAPK in HCAECs. These findings show that atorvastatin suppresses endothelial cell inflammation, suggesting that atorvastatin may be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.

Protective Effect of Se-Methylselenocysteine on Elaidic Acid-Induced Inflammation in Human Arterial Endothelial Cells.

This study was designed to investigate the anti-inflammatory effect of Se-methylselenocysteine (MSC) on elaidic acid (9t18:1, EA) induced human arterial endothelial cells (HAECs). MTT and flow cytometry were used to determine cell viability and cell apoptosis respectively. Western blotting was used to assess protein expression of intercellular adhesion molecular 1 (ICAM-1), E-selectin, interleukin-8 (IL-8), endothelial nitric oxide synthase (e-NOS) and phospholipases A2 (PLA2), while enzyme-linked immunosorbent assay (ELISA) was performed to examine the secretion level of nitric oxide (NO). In the cell viability assay, EA significantly decreased cell viability when compared with negative control (NC) group, and MSC effectively reversed this adverse effect, especially at the concentration of 200 μmol/L with 24 h incubation. Also, the same concentration of MSC prevented HAECs cell apoptosis induced by EA. In addition, we found that the expression of ICAM-1, E-selectin, IL-8 and PLA2 were significantly increased and e-NOS decreased in EA group compared with NC group. Inhibition of PLA2 promoted ICAM-1, E-slectin and IL-8 expression in HAECs induced by EA. And MSC down-regulated the secretion of NO level in EA-induced HAECs. Based on these results, we concluded that MSC activated PLA2 which regulated the expression of ICAM-1, E-selectin and IL-8 to protect inflammation induced by EA in HEACs.

Expression and significance of COX-2, ICAM-1 and IFN- γ in serum of rats with chronic prostatitis

Objective To investigate the expression and significance of Cyclooxygenase-2 (COX-2), Intercellular adhesion molecular-1 (ICAM-1), Interferon-γ(IFN-γ) in serum of chronic prostatitis rats. Methods Forty-five male Wistar rats were randomly divided into the control group and the model group, which were provided by the animal research center of Jiamusi university. The model group was constructed with the model of chronic prostatitis. The expression level of COX-2 protein, ICAM-1 protein and IFN-γ protein was detected by Western blot, and the expression level of COX-2 mRNA, ICAM-1 mRNA and IFN-gamma mRNA was detected by RT-PCR. Results The expression of COX-2, ICAM-1, IFN-γ protein and mRNA in the control group and the model group were consistent. The expression level of COX-2 protein and COX-2 mRNA in the model group was significantly higher than that in the control group(P<0.05), and the expression level of ICAM-1 protein and ICAM-1 mRNA in the model group was significantly higher than that of the control group(P<0.05), and the expression level of IFN-γ protein and IFN-γ mRNA in the model group was significantly higher than that of the control group(P<0.05). The sensitivity of the three indexes was detected. Sensitivity, specificity and accuracy were all higher than those of the other two items. The sensitivity, specificity and accuracy of the three joint tests were significantly higher than those of the single test, with a statistically significant difference(P<0.05). The expression of prostaglandin increased with the increase of COX-2 expression, and the different stages of chronic prostatitis also had an effect on its secretion. Conclusions The changes of expression level of COX-2, ICAM-1 and IFN-γ are closely related to chronic prostatitis. It is very important for the diagnosis, treatment and prognosis of chronic prostatitis to monitor the changes of expression level of COX-2, ICAM-1 and IFN-γ. Key words: Prostatitis; Models, Animal; Cyclooxygenase 2; Junctional Adhesion Molecules; Interferon-gamma

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium.

The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b+ cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect.

Intercellular Adhesion Molecular-1, Fas, and Fas Ligand as Diagnostic Biomarkers for Acute Allograft Rejection of Pancreaticoduodenal Transplantation in Pigs

The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.

Poly(ADP-ribose) polymerase 1 inhibition protects against low shear stress induced inflammation

Background: Atherosclerosis begins as local inflammation of vessels at sites of disturbed flow, where low shear stress (LSS) leads to mechanical irritation and plaque development and progression. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is associated with the inflammation response during atherosclerosis. We investigated the role and underlying mechanism of PARP-1 in LSS-induced inflammation in human umbilical vein endothelial cells (HUVECs). Methods and results: HUVECs were simulated by LSS (0.4Pa). PARP-1 expression was inhibited by ABT888 or siRNA. The inducible nitric oxide synthase (iNOS) and intercellular adhesion molecular-1 (ICAM-1) expression was regulated by LSS in a time dependent manner. LSS could increase superoxide production and 3-nitrotyrosine formation. LSS induced DNA damage as assessed by H2A.X phosphorylation and comet assay. Compared with cells under static, LSS increased PARP-1 expression and PAR formation via MEK/ERK signaling pathway. PARP-1 inhibition increased Sirt1 activity through an increased intracellular nicotinamide adenine dinucleotide (NAD+) level. Moreover, PARP-1 inhibition attenuated LSS-induced iNOS and ICAM-1 upregulation by inhibiting nuclear factor kappa B (NF-κB) nuclear translocation and activity, with a reduced NF-κB phosphorylation. Conclusions: LSS induced oxidative damage and PARP-1 activation via MEK/ERK pathway. PARP-1 inhibition restored Sirt1 activity by increasing NAD+ level and decreased iNOS and ICAM-1 expression by inhibiting NF-κB nuclear translocation and activity as well as NF-κB phosphorylation. PARP-1 played a fundamental role in LSS induced inflammation. Inhibition of PARP-1 might be a mechanism for treatment of inflammation response during atherosclerosis.

β2-Agonists Inhibit TNF-α-Induced ICAM-1 Expression in Human Airway Parasympathetic Neurons

BackgroundMajor basic protein released from eosinophils to airway parasympathetic nerves blocks inhibitory M2 muscarinic receptors on the parasympathetic nerves, increasing acetylcholine release and potentiating reflex bronchoconstriction. Recruitment of eosinophils to airway parasympathetic neurons requires neural expression of both intercellular adhesion molecular-1 (ICAM-1) and eotaxin. We have shown that inflammatory cytokines induce eotaxin and ICAM-1 expression in parasympathetic neurons.ObjectiveTo test whether the β2 agonist albuterol, which is used to treat asthma, changes TNF-alpha-induced eotaxin and ICAM-1 expression in human parasympathetic neurons.MethodsParasympathetic neurons were isolated from human tracheas and grown in serum-free medium for one week. Cells were incubated with either (R)-albuterol (the active isomer), (S)-albuterol (the inactive isomer) or (R,S)-albuterol for 90 minutes before adding 2 ng/ml TNF-alpha for another 4 hours (for mRNA) or 24 hours (for protein).Results and ConclusionsBaseline expression of eotaxin and ICAM-1 were not changed by any isomer of albuterol as measured by real time RT-PCR. TNF-alpha induced ICAM-1 expression was significantly inhibited by (R)-albuterol in a dose dependent manner, but not by (S) or (R,S)-albuterol. Eotaxin expression was not changed by TNF-alpha or by any isomer of albuterol. The β-receptor antagonist propranolol blocked the inhibitory effect of (R)-albuterol on TNF-alpha-induced ICAM-1 expression.Clinical ImplicationThe suppressive effect of (R)-albuterol on neural ICAM-1 expression may be an additional mechanism for decreasing bronchoconstriction, since it would decrease eosinophil recruitment to the airway nerves.

Crocetin inhibits leukocyte adherence to vascular endothelial cells induced by AGEs

Advance glycation end products (AGEs) have been postulated to play an important role in diabetic complications such as atherosclerosis disease. Adhesion and migration of leukocyte to endothelial cells (EC) is one of the early key steps in the pathogenesis. Crocetin is an important ingredient of diet in India and also used in various systems of indigenous medicine. In this study, we investigated effect of crocetin on leukocyte adherence to bovine endothelial cells (BEC) induced by AGEs in vitro and the possible mechanisms involved. BEC were pre-incubated with crocetin (0.01, 0.1, and 1 μM) for 12 h and exposed to AGEs (100 μg/ml). Cells proliferation was determined by MTT; leukocyte–endothelial cell adhesion was assayed by myeloperoxidase methods; intercellular adhesion molecular-1 (ICAM-1) protein expression was studied by immunocytochemistry and mitochondrial membrane potential (MMP) was analyzed by the retention of rhodamine 123 (RH123); furthermore, levels of anion (O 2 −), malonicdialdehyde (MDA) in super cells culture and superoxide dismutase (SOD) in cells were also detected, respectively. Results demonstrated that crocetin could inhibit AGE-induced BEC growth suppression and significantly reduce adhesion rate of leukocyte to BEC ( P < 0.01 or P < 0.05); ICAM-1 protein was also suppressed ( P < 0.05). Furthermore, crocetin could increase activity of SOD ( P < 0.05), decrease levels of MDA and O 2 − ( P < 0.01). In addition, down-regulated MMP was also increased by crocetin ( P < 0.01 or P < 0.05). These data revealed crocetin could prevent the adhesion of leukocyte to BEC and down-regulation the expression of ICAM-1, and the possible mechanisms might be related to its antioxidant activity, which is through up-regulation of the activity of antioxidant enzymes and protection for mitochondrion.

Inhibitory influences of xanthine oxidase inhibitor and angiotensin I-converting enzyme inhibitor on multinucleated giant cell formation from monocytes by downregulation of adhesion molecules and purinergic receptors.

Allopurinol, a xanthine oxidase inhibitor, and captopril, an inhibitor of angiotensin I-converting enzyme, are widely used for hyperuricaemia and hypertension, respectively. There have been reported cases showing that these two agents are effective for the treatment of granulomatous diseases such as sarcoidosis, although the mode of action is not elucidated. We examined the in vitro effects of these agents on the formation of multinucleated giant cells (MGC) from human monocytes by concanavalin A-stimulated mononuclear cell supernatants (conditioned medium). We cultured monocytes with conditioned medium and each agent and compared the rate of MGC formation as well as the expression of adhesion molecules and P2X7 receptor, which are involved in MGC formation. The addition of 25 or 100 microg mL(-1) allopurinol or 0.125-1.0 microg mL(-1) captopril inhibited MGC formation. Monocytes treated with these agents exhibited less expression of intercellular adhesion molecular-1 (ICAM-1) than untreated monocytes. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2'-and 3'-o-(4-benzoyl-benzoyl)adenosine triphosphate-mediated cytolysis was significantly lower in monocytes treated with these agents than in untreated monocytes. Allopurinol and captopril have a therapeutic effect on granulomatous disorders by a direct action on monocyte/macrophage lineage cells partly through downregulation of ICAM-1 and P2X7 receptor.

Nicotine- and arecoline-induced interleukin-1 secretion and intercellular adhesion molecular-1 expression in human oral epidermoid carcinoma cells in vitro

The purpose was to examine interleukin (IL)-1 concentrations and intercellular adhesion molecule (ICAM)-1 expression in nicotine/arecoline-exposed oral KB CCL17 cultures. Enzyme-linked immunosorbent assay was used to quantify IL-1 concentrations in culture supernatants. A repeated-measures analysis of variance was used to identify differences among the groups. IL-1 β concentrations increased by 2.6, 2.7 and 7.5 times those of the control in groups treated with 1 μM nicotine, arecoline or with both, respectively. IL-1 β concentrations were more dramatically increased when the agents tested were at 100 μM concentration. Similar, although less dramatic, alterations in IL-1 α concentrations were observed. The fluorescence intensity of ICAM-1 (CD54) analysed by flow cytometry was also significantly increased in a dose-dependent manner when the cells were treated with nicotine and/or arecoline. Nicotine and arecoline therefore significantly increased IL-1 α and -1 β secretions and the surface expression of ICAM-1 in KB CCL17 cells.