Intercellular Adhesion Molecule-1 Protein Research Articles

Rose Bengal Photodynamic Therapy (RB-PDT) Modulates the Inflammatory Response in LPS-Stimulated Human Corneal Fibroblasts By Influencing NF-κB and p38 MAPK Signaling Pathways

Purpose To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. Methods Human corneal fibroblast cultures underwent 0–2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0.17 J/cm2 fluence). Interleukin-6, interleukin-8, intercellular adhesion molecule-1, interferon regulatory factor-3, interferon α2, and interferon β1 gene expressions were determined by quantitative PCR. Interleukin-6, interleukin-8, and C-C motif chemokine ligand-4 concentrations in the cell culture supernatant were measured by enzyme-linked immunosorbent assays and intercellular adhesion molecule-1 protein level in human corneal fibroblasts by western blot. In addition, the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways were investigated by quantitative PCR and phosphorylation of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase by western blot. Results Rose bengal photodynamic therapy in 2.0 µg/mL lipopolysaccharide-stimulated human corneal fibroblasts triggered interleukin-6 and interleukin-8 mRNA (p < .0001) and interleukin-6 protein increase (p < .0001), and downregulated intercellular adhesion molecule-1 expression (p < .001). C-C motif chemokine ligand-4, interferon regulatory factor-3, interferon α2, and interferon β1 expressions remained unchanged (p ≥ .2). Rose bengal photodynamic therapy increased IκB kinase subunit beta, nuclear factor kappa B p65, extracellular signal-regulated kinases-2, c-Jun amino terminal kinase, and p38 transcription (p ≤ .01), and triggered nuclear factor kappa B p65 and p38 mitogen-activated protein kinase phosphorylation (p ≤ .04) in lipopolysaccharide treated human corneal fibroblasts. Conclusion Rose bengal photodynamic therapy of lipopolysaccharide-stimulated human corneal fibroblasts can modify the inflammatory response by inducing interleukin-6 and interleukin-8 expression, and decreasing intercellular adhesion molecule-1 production. C-C motif chemokine ligand-4, interferon regulatory factor-3, and interferon α and β expressions are not affected by rose bengal photodynamic therapy in these cells. The underlying mechanisms may be associated with nuclear factor kappa B and p38 mitogen-activated protein kinase pathway activation.

Brief research report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells

Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting ICAM1 gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of ICAM1 gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells. We first examined ICAM1 and ETS1 transcript expression in human retinal endothelial cells exposed to tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β). ICAM1 and ETS1 transcripts were increased in parallel in primary human retinal endothelial cell isolates (n = 5) after a 4-hour stimulation with TNF-α or IL-1β (p ≤ 0.012 and ≤ 0.032, respectively). We then assessed the effect of ETS-1 blockade by small interfering (si)RNA on cellular ICAM1 transcript and membrane-bound ICAM-1 protein. ETS1 transcript was reduced by greater than 90% in cytokine-stimulated and non-stimulated human retinal endothelial cell monolayers following a 48-hour treatment with two ETS-1-targeted siRNA, in comparison to negative control non-targeted siRNA (p ≤ 0.0002). The ETS-1 blockade did not reduce ICAM1 transcript expression nor levels of membrane-bound ICAM-1 protein, rather it increased both for a majority of siRNA-treatment and cytokine-stimulation conditions (p ≤ 0.018 and ≤ 0.004, respectively). These unexpected findings indicate that ETS-1 blockade increases ICAM-1 transcript and protein levels in human retinal endothelial cells. Thus ETS-1-targeting would be expected to promote rather than inhibit retinal transendothelial migration of leukocytes in non-infectious posterior uveitis.

Intercellular Adhesion Molecule 1: More than a Leukocyte Adhesion Molecule.

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.

In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion.

Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Neutrophil-Membrane-Coated Biomineralized Metal-Organic Framework Nanoparticles for Atherosclerosis Treatment by Targeting Gene Silencing.

Antisense oligonucleotides (ASOs) are promising tools for gene silencing and have been exploited as therapeutics for human disease. However, delivery of therapeutic ASOs to diseased tissues or cells and subsequent escape from the endosomes and release of ASO in the cytosol remain a challenge. Here, we reported a neutrophil-membrane-coated zeolitic imidazolate framework-8 (ZIF-8) nanodelivery platform (AM@ZIF@NM) for the targeted transportation of ASOs against microRNA-155 (anti-miRNA-155) to the endothelial cells in atherosclerotic lesions. Neutrophil membrane could improve plaque endothelial cells targeting through the interaction between neutrophil membrane protein CD18 and endothelial cell membrane protein intercellular adhesion molecule-1 (ICAM-1). The ZIF-8 "core" provided high loading capacity and efficient endolysosomal escaping ability. Delivery of anti-miR-155 effectively downregulated miR-155 expression and also saved the expression of its target gene BCL6. Moreover, RELA expression and the expression of its downstream target genes CCL2 and ICAM-1 were correspondingly reduced. Consequently, this anti-miR-155 nanotherapy can inhibit the inflammation of atherosclerotic lesions and alleviate atherosclerosis. Our study shows that the designed biomimetic nanodelivery system has great application prospects in the treatment of other chronic diseases.

Acupuncture affects the apoptosis of eosinophilic granulocytes in lung tissue of asthmatic rats by regulating the P38MAPK signaling pathway

To investigate the effects of acupuncture on phosphorylated P38 mitogen-activated protein kinase (p-P38MAPK), intercellular adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), and eosinophilic granulocytes (EOS) in lung tissue of asthmatic rats, and to explore the mechanism of acupuncture in regulating the apoptosis of EOS. Clean-grade male Wistar rats were randomly divided into normal, model, dexamethasone and acupuncture groups, 8 rats in each group. The asthmatic model was established by intraperitoneal injection of mixture suspension (1 mL) of 10% ovalbumin and 10% Al(OH)_3+ normal saline, followed by inhalation of atomized 1% ovalbumin solution for 30 min, once daily for 2 weeks to trigger occurrence of asthmatic symptoms. The rats in dexamethasone group were intraperitoneally injected with 0.9 mg/kg dexamethasone since day 15 once a day for two consecutive weeks. In the acupuncture group, bilateral "Feishu" (BL13), "Pishu" (BL20), "Shenshu" (BL23), "Dingchuan" (EX-B1), and "Danzhong" (CV17) were selected for acupuncture treatment once every other day since day 15 for two consecutive weeks. Uniform reinforcing and reducing manipulation was carried out, and the needles were retained for 30 min. The pathological changes of the lung tissue were observed by hematoxylin-eosin (HE) staining. The apoptosis of EOS in the lung tissue of rats was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of p-P38MAPK in the lung tissue was detected by Western blot. The protein and mRNA levels of ICAM-1 and IFN-γ in the lung tissue were determined by immunohistochemistry and real-time PCR, respectively. The results of HE staining showed that the pulmonary alveoli and surrounding tissues were intact with no inflammatory cell infiltration in the normal group. The model group showed massive exudation of inflammatory materials and thickened pulmonary interstitium. The dexamethasone group and acupuncture group showed less damage of the alveolar structure and only a small number of inflammatory cells around the airway. Compared with the normal group, the apoptosis rate of EOS in lung tissue was decreased (P<0.01), the expression levels of p-P38MAPK and ICAM-1 proteins and mRNAs in the lung tissue were up-regulated (P<0.01), while the expression levels of IFN-γ protein and mRNA in the lung tissue were down-regulated (P<0.01) in the model group. Compared with the model group, the apoptosis rate of EOS in the lung tissue was increased (P<0.05), the expression levels of p-P38MAPK and ICAM-1 proteins and mRNAs in the lung tissue were down-regulated (P<0.01, P<0.05), while the expression levels of IFN-γ protein and mRNA were up-regulated (P<0.05, P<0.01) in the dexamethasone and acupuncture groups. Acupuncture may inhibit the P38MAPK signaling pathway, down-regulate ICAM-1 expression, and up-regulate IFN-γ expression to promote the apoptosis of EOS and reduce EOS aggregation, thus alleviating the inflammatory response of airway in asthma.

Inhibition of Vascular Inflammation by Apolipoprotein A-IV.

BackgroundApolipoprotein (apo) A-IV, the third most abundant apolipoprotein in human high density lipoproteins (HDLs), inhibits intestinal and systemic inflammation. This study asks if apoA-IV also inhibits acute vascular inflammation.MethodsInflammation was induced in New Zealand White rabbits by placing a non-occlusive silastic collar around the common carotid artery. A single 1 mg/kg intravenous infusion of lipid-free apoA-IV or saline (control) was administered to the animals 24 h before collar insertion. The animals were euthanised 24 h post-collar insertion. Human coronary artery cells (HCAECs) were pre-incubated with reconstituted HDLs containing apoA-IV complexed with phosphatidylcholine, (A-IV)rHDLs, then activated by incubation with tumour necrosis factor (TNF)-α. Cell surface vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the TNF-α-activated HCAECs was quantified by flow cytometry. VCAM-1, ICAM-1 and 3β-hydroxysteroid-Δ24 reductase (DHCR24) mRNA levels were quantified by real time PCR.ResultsApolipoprotein ApoA-IV treatment significantly decreased collar-induced endothelial expression of VCAM-1, ICAM-1 and neutrophil infiltration into the arterial intima by 67.6 ± 9.9% (p < 0.01), 75.4 ± 6.9% (p < 0.01) and 74.4 ± 8.5% (p < 0.05), respectively. It also increased endothelial expression of DHCR24 by 2.6-fold (p < 0.05). Pre-incubation of HCAECs with (A-IV)rHDLs prior to stimulation with TNF-α inhibited VCAM-1 and ICAM-1 protein levels by 62.2 ± 12.1% and 33.7 ± 5.7%, respectively. VCAM-1 and ICAM-1 mRNA levels were decreased by 55.8 ± 7.2% and 49.6 ± 7.9%, respectively, while DHCR24 mRNA expression increased by threefold. Transfection of HCAECs with DHCR24 siRNA attenuated the anti-inflammatory effects of (A-IV)rHDLs. Pre-incubation of TNF-α-activated HCAECs with (A-IV)rHDLs also inhibited nuclear translocation of the p65 subunit of nuclear factor-κB (NF-κB), and decreased IκBα phosphorylation.ConclusionThese results indicate that apoA-IV inhibits vascular inflammation in vitro and in vivo by inhibiting NF-κB activation in a DHCR24-dependent manner.

Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats

Exogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing transforming growth factor-β-activated kinase 1 (TAK1) and reactive oxygen species (ROS)-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6h after the occurrence of facial paralysis and peaked after 2days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells

BackgroundPrior studies show that signature phenotypes of diabetic human induced pluripotent stem cells derived endothelial cells (dia-hiPSC-ECs) are disrupted glycine homeostasis, increased senescence, impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. In the current study, we aimed to assess the role of thymosin β-4 (Tb-4) on endothelial function using dia-hiPSC-ECs as disease model of endothelial dysfunction.Methods and resultsUsing dia-hiPSC-ECs as models of endothelial dysfunction, we determined the effect of Tb-4 on cell proliferation, senescence, cyto-protection, protein expression of intercellular adhesion molecule-1 (ICAM-1), secretion of endothelin-1 and MMP-1, mitochondrial membrane potential, and cyto-protection in vitro and angiogenic potential for treatment of ischemic limb disease in a mouse model of type 2 diabetes mellitus (T2DM) in vivo. We found that 600 ng/mL Tb4 significantly up-regulated AKT activity and Bcl-XL protein expression, enhanced dia-hiPSC-EC viability and proliferation, limited senescence, reduced endothelin-1 and MMP-1 secretion, and improved reparative potency of dia-hiPSC-ECs for treatment of ischemic limb disease in mice with T2DM. However, Tb4 had no effect on improving mitochondrial membrane potential and glycine homeostasis and reducing intercellular adhesion molecule-1 protein expression in dia-hiPSC-ECs.ConclusionsTb-4 improves endothelial dysfunction through enhancing hiPSC-EC viability, reducing senescence and endothelin-1 production, and improves angiogenic potency in diabetes.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC.

Effect of butyrate, a bacterial by-product, on the viability and ICAM-1 expression/production of human vascular endothelial cells: Role in infectious pulpal/periapical diseases.

To investigate the effects of butyric acid (BA), a metabolic product generated by pulp and root canal pathogens, on the viability and intercellular adhesion molecule-1 (ICAM-1) production of endothelial cells, which are crucial to angiogenesis and pulpal/periapical wound healing. Endothelial cells were exposed to butyrate with/without inhibitors. Cell viability, apoptosis and reactive oxygen species (ROS) were evaluated using an MTT assay, PI/annexin V and DCF fluorescence flow cytometry respectively. RNA and protein expression was determined using a polymerase chain reaction assay and Western blotting or immunofluorescent staining. Soluble ICAM-1 (sICAM-1) was measured using an enzyme-linked immunosorbent assay. The quantitative results were expressed as mean±standard error (SE) of the mean. The data were analysed using a paired Student's t-test where necessary. A p-value ≤0.05 was considered to indicate a statistically significant difference between groups. Butyrate (>4mM) inhibited cell viability and induced cellular apoptosis and necrosis. It inhibited cyclin B1 but stimulated p21 and p27 expression. Butyrate stimulated ROS production and hemeoxygenase-1 (HO-1) expression as well as activated the Ac-H3, p-ATM, p-ATR, p-Chk1, p-Chk2, p-p38 and p-Akt expression of endothelial cells. Butyrate stimulated ICAM-1mRNA/protein expression and significant sICAM-1 production (p<.05). Superoxide dismutase, 5z-7oxozeaenol, SB203580 and compound C (p<.05), but not ZnPP, CGK733, AZD7762 or LY294002, attenuated butyrate cytotoxicity to endothelial cells. Notably, little effect on butyrate-stimulated sICAM-1secretion was found. Valproic acid, phenylbutyrate and trichostatin (three histone deacetylase inhibitors) significantly induced sICAM-1 production (p<.05). Butyric acid inhibited proliferation, induced apoptosis, stimulated ROS and HO-1 production and increased ICAM-1mRNA expression and protein synthesis in endothelial cells. Cell viability affected by BA was diminished by some inhibitors; however, the increased sICAM-1secretion by BA was not affected by any of the tested inhibitors. These results facilitate understanding of the pathogenesis, prevention and treatment of pulpal/periapical diseases.

Propofol Inhibits Lung Cancer Invasion and Metastasis by Attenuating Icam-1/ Mmp-9 Axis

Objective: To investigate the effect of propofol on invasion and metastasis of A549 cells and the expression of intercellular adhesion molecule 1 (ICAM-1) / matrix metalloproteinase-9 (MMP-9) axis.Methods: A549 cells were treated with gradient doses of propofol (25, 50, 100 ng/ml) and different times (12, 24 h). The influences of propofol on ICAM-1 mRNA of A549 cells were observed by qRT-PCR, and the roles of different concentrations of propofol on ICAM-1 and MMP-9 protein and invasion ability were detected by Western Blot and Transwell assay, respectively.Results: The maximum inhibitory influence of propofol was achieved in group 100μg/ml for 24 h. ICAM-1 and MMP-9 protein in the treatment group with 25, 50 and 100μg/ml propofol for 24 h were significantly lower than those in the control group. The number of migrated and invaded cells in the 25, 50 and 100 ng/ml propofol treatment group for 24 h was significantly lower than that in the blank group.Condusion: ICAM-1 protein and MMP-9 protein in human lung cancer A549 cells could be down-regulated after treatment with 50 and 100μg/ml propofol, and the invasion and metastasis ability of A549 cells could be attenuated through ICAM-1/MMP-9 axis.

Inhibition of cell migration and invasion by ICAM-1 binding DNA aptamers

Cancer is the second leading cause of death worldwide and most of the cancer-related deaths result from metastasis. As expressed on the surface of various cancer cell types, intercellular adhesion molecule-1 (ICAM-1) has been shown to play a role in the attachment, invasion and migration of tumor cells. In this study, DNA aptamers were generated against ICAM-1 by cell-SELEX and protein SELEX method using ICAM-1(+) CHO-ICAM-1 cells and ICAM-1 protein, respectively. The pools obtained at the end of the 10th round of both SELEX were sequenced and the most enriched sequences were characterized for their binding behaviors and affinities to ICAM-1(+) CHO-ICAM-1 and ICAM-1(−) MIA PaCa-2 cells. Moreover, the inhibition abilities of sequences on migration and invasion were measured. The seven aptamer sequences were obtained selectively binding to CHO-ICAM-1 cells with Kd values in the ranging from 13.8 to 47.1 nM. Four of these aptamers showed inhibition in both migration and invasion of CHO-ICAM-1 cells at least 61%. All these results suggested that these aptamers have potential to detect specifically ICAM-1 expressing tumor cells and inhibit migration and invasion by blocking ICAM-1 related interactions of circulating tumor cells.

Resolvin D1 and E1 promote resolution of inflammation in rat cardiac fibroblast in vitro.

Cardiac fibroblasts (CFs) have a key role in the inflammatory response after cardiac injury and are necessary for wound healing. Resolvins are potent agonists that control the duration and magnitude of inflammation. They decrease mediators of pro-inflammatory expression, reduce neutrophil migration to inflammation sites, promote the removal of microbes and apoptotic cells, and reduce exudate. However, whether resolvins can prevent pro-inflammatory-dependent effects in CFs is unknown. Thus, the present work was addressed to study whether resolvin D1 and E1 (RvD1 and RvE1) can prevent pro-inflammatory effects on CFs after lipopolysaccharide (LPS) challenge. For this, CFs were stimulated with LPS, in the presence or absence of RvD1 or RvE1, to analyze its effects on intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), monocyte adhesion and the cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10). Our results showed that CFs are expressing ALX/FPR2 and ChemR23, RvD1 and RvE1 receptors, respectively. RvD1 and RvE1 prevent the increase of ICAM-1 and VCAM-1 protein levels and the adhesion of spleen mononuclear cells to CFs induced by LPS. Finally, RvD1, but not RvE1, prevents the LPS-induced increase of IL-6, MCP-1, TNF-α, and IL-10. In conclusion, our findings provide evidence that in CFs, RvD1 and RvE1 might actively participate in the prevention of inflammatory response triggered by LPS.

α-Conidendrin inhibits the expression of intercellular adhesion molecule-1 induced by tumor necrosis factor-α in human lung adenocarcinoma A549 cells

α-Conidendrin is a lignan isolated from Taxus wallichiana and other species. In the present study, we demonstrated that α-conidendrin inhibited the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-α (TNF-α) at an IC50 value of 40–60 μM in human lung adenocarcinoma A549 cells. α-Conidendrin decreased ICAM-1 protein and mRNA expression levels at concentrations of 40–100 μM in TNF-α-stimulated A549 cells. The TNF-α-induced mRNA expression of vascular cell adhesion molecule-1, E-selectin, and cyclooxygenase-2 was also reduced by α-conidendrin. In the TNF-α-induced nuclear factor κB (NF-κB) signaling pathway, α-conidendrin did not influence the translocation of the NF-κB subunit RelA from the cytoplasm to the nucleus at concentrations up to 100 μM. A chromatin immunoprecipitation assay revealed that α-conidendrin at 100 μM reduced the binding of RelA to the ICAM-1 promoter in response to a stimulation with TNF-α. Collectively, these results indicated that α-conidendrin interfered with the DNA binding of RelA to the ICAM-1 promoter, thereby reducing ICAM-1 transcription.

Visfatin increases ICAM-1 expression and monocyte adhesion in human osteoarthritis synovial fibroblasts by reducing miR-320a expression.

Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include monocyte adhesion and infiltration, and synovial inflammation. In particular, the adhesion protein intercellular adhesion molecule type 1 (ICAM-1) promotes monocyte recruitment into the synovial tissue. Visfatin is an adipocyte hormone that promotes the release of inflammatory cytokines during OA progression. We report that visfatin enhances ICAM-1 expression in human OA synovial fibroblasts (OASFs) and facilitates the adhesion of monocytes with OASFs. AMPK and p38 inhibitors, as well as their respective siRNAs, attenuated the effects of visfatin upon ICAM-1 synthesis and monocyte adhesion. We also describe how miR-320a negatively regulates visfatin-induced promotion of ICAM-1 expression and monocyte adhesion. We detail how visfatin affects ICAM-1 expression and monocyte adhesion with OASFs by inhibiting miR-320a synthesis via the AMPK and p38 signaling pathways.

Detection of Lipase Activity in Cells by a Fluorescent Probe Based on Formation of Self-Assembled Micelles.

SummaryReliable and sensitive detection of lipase activity is essential for the early diagnosis and monitoring of acute pancreatitis or progression of digestive diseases. However, the available fluorescent probes for detection of lipase activity are only implemented in a hexane-water two-phase system due to the nature of heterogeneous catalysis of lipase, thus limiting their applications in direct imaging of lipase activity in living cells and tissues. Here we designed and synthesized a “turn on” fluorescent probe CPP based on self-assembled micelles for hydrolysis of lipase. The CPP probe exhibits high selectivity and excellent sensitivity for the detection of lipase in such a homogeneous system and is successfully applied for monitoring lipase activity in pancreatic AR42J cells, tissues, and serums. Taken together, the fluorescent CPP probe not only provides a tool for diagnostic potential in pancreatic disease but also demonstrates an application potential for micelle self-assembly-based development of biological probes.

Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.

A Allele of ICAM-1 Rs5498 and VCAM-1 Rs3181092 is Correlated with Increased Risk for Periodontal Disease.

ObjectivePeriodontal disease (PD) is viewed today as multifactorial problems initiated and sustained by bacteria but significantly modified by the body’s response to bacterial plaque. Recent studies have suggested that gene polymorphisms could be involved in the pathophysiology of periodontitis. This study aimed to investigate a possible correlation of the polymorphisms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with PD.MethodsThe genotypes of ICAM-1 and VCAM-1 were initially determined in PD patients using denaturing high performance liquid chromatography (DHPLC). ELISA was then conducted to measure ICAM-1 and VCAM-1 protein levels. Next, the association of ICAM-1/VCAM-1 genotype distribution and expression with clinical indicators and severity of PD was analyzed.ResultsPD patients contained increased levels of hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), increased ICAM-1 and VCAM-1 protein levels, and decreased high-density lipoprotein (HDL) level. The GG genotype and G allele at ICAM-1 rs5498, as well as the AG and GG genotypes and G allele at VCAM-1 rs3181092 may reduce PD risk.ConclusionTo sum up, the overexpressed ICAM-1 and VCA M-1 as well as A allele of ICAM-1 rs5498 and VCAM-1 rs3181092 is associated with the onset of PD.