scholarly journals Mediation by NF-κB of cytokine induced expression of intercellular adhesion molecule 1 (ICAM-1) in an intestinal epithelial cell line, a process blocked by proteasome inhibitors

Gut ◽  
1998 ◽  
Vol 42 (6) ◽  
pp. 779-787 ◽  
Author(s):  
C Jobin ◽  
C Hellerbrand ◽  
L L Licato ◽  
D A Brenner ◽  
R B Sartor
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Nuclear Translocation ◽  
Proteasome Inhibitors ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Iκbα Degradation

Background/aims—The gene promoter for the intercellular adhesion molecule ICAM-1 possesses binding sites for several transcriptional factors, including nuclear factor κB (NF-κB). The role of NF-κB in ICAM-1 gene regulation was therefore examined by using different proteasome inhibitors in tumour necrosis factor α (TNF-α) stimulated IEC-6 rat intestinal epithelial cells.Methods—ICAM-1 expression was analysed by enzyme linked immunosorbent assay (ELISA), reverse transcriptase polymerase chain reaction, and immunohistochemistry. Steady state levels of cytoplasmic IκB protein were evaluated by western blot, and nuclear translocation of NF-κB was determined by electrophoretic mobility shift assay and immunofluorescence staining. Cell adhesion was assayed by measuring the binding of fluorescence labelled MOLT-4 cells.Results—TNF-α induced ICAM-1 mRNA and protein expression in IEC-6 cells, which was followed by increased adhesion of MOLT-4 lymphocytes. Blocking TNF-α induced IκBα degradation with proteasome inhibitors reduced TNF-α induced NF-κB activation and ICAM-1 gene induction and notably decreased MOLT-4 cell adhesion without affecting Jun N-terminal kinase (JNK/SAPK) activity or de novo protein synthesis.Conclusion—TNF-α induction of ICAM-1 expression is mediated by the transcription factor NF-κB and can be inhibited by blocking IκBα degradation. Thus the IκB/NF-κB system is a promising target for pharmacological modulation of the expression of adhesion molecules and other inflammatory genes in the intestine.

Green Tea Polyphenol Epigallocatechin-3-Gallate Attenuates TNF-α-Induced Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Retinal Pigment Epithelial Cells

2015 ◽  
Vol 43 (01) ◽  
pp. 103-119 ◽  
Author(s):  
Peeradech Thichanpiang ◽  
Kanokpan Wongprasert
Keyword(s):  
Green Tea ◽  
Adhesion Molecule ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Intercellular Adhesion ◽  
Laser Scanning Microscopy ◽  
Leukocyte Migration ◽  
Intercellular Adhesion Molecule ◽  
Tnf Α ◽  
Anti Inflammatory

Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea (Camellia sinensis) and demonstrates anti-oxidant, anticancer and anti-inflammatory properties. EGCG has been shown to protect retinal pigment epithelium (RPE) against oxidative stress-induced cell death. The pathogenesis of diseases in the retina is usually initiated by local inflammation at the RPE cell layer, and inflammation is mostly associated with leukocyte migration and the secretion of pro-inflammatory cytokines. Whether EGCG can modulate the cytokine-induced inflammatory response of RPE, particularly leukocyte migration, has not been clearly elucidated, and was therefore the objective of this study. ARPE-19 cells were cultured with different concentrations of TNF-α in the presence or absence of EGCG to different time points. Intracellular reactive oxygen species (ROS) levels were determined. Intercellular adhesion molecule (ICAM)-1 and phosphor-NF-κB and IκB expression were determined by Western blot analysis. Phosphor-NF-κB nuclear translocation and monocyte–RPE adhesion were investigated using immunofluorescence confocal laser scanning microscopy. Scanning electron microscopy (SEM) was carried out to further determine the ultrastructure of monocyte–RPE adhesion. The results demonstrated that TNF-α modulated inflammatory effects in ARPE-19 by induction of ROS and up-regulation of ICAM-1 expression. Moreover, TNF-α-induced phosphor-NF-κB nuclear translocation, increased phosphor-NF-κB expression and IκB degradation, and increased the degree of monocyte–RPE adhesion. Pretreating the cells with EGCG ameliorated the inflammatory effects of TNF-α. The results indicated that EGCG significantly exerts anti-inflammatory effects in ARPE-19 cells, partly as a suppressor of TNF-α signaling and that the inhibition was mediated via the NF-κB pathway.

scholarly journals Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença

2010 ◽  
Vol 36 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Renata Amato Vieira ◽  
Edna Maria de Albuquerque Diniz ◽  
Maria Esther Jurfest Rivero Ceccon
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Tnf Α ◽  
Soluble Intercellular Adhesion Molecule ◽  
Molecule Type

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

Circulating forms of intercellular adhesion molecule (ICAM)-1 in mice lacking membranous ICAM-1

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1350-1355 ◽  
Author(s):  
Natasja K. van den Engel ◽  
Edmund Heidenthal ◽  
Antje Vinke ◽  
Hubert Kolb ◽  
Stephan Martin
Keyword(s):  
Adhesion Molecule ◽  
Transmembrane Domain ◽  
Flow Cytometric Analysis ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immune Functions ◽  
Wild Type ◽  
Spleen Cells ◽  
Intercellular Adhesion Molecule 1

Mice deficient in intercellular adhesion molecule-1 (ICAM-1), lacking membranous ICAM-1, show a normal development but abnormalities of inflammatory and immune functions. Although the membrane-bound form of ICAM-1 is not detectable in the mutant strain, circulating ICAM-1 (cICAM) is present in serum from ICAM-1-deficient mice in similar amounts as in serum from wild-type mice. These findings were confirmed in vitro by flow cytometric analysis of lipopolysaccharide-stimulated spleen cells, and cICAM-enzyme-linked immunosorbent assay analysis of supernatants of cultured spleen cells. To analyze for the source of cICAM-1, spleen cell RNA was isolated and ICAM-1 RNA was amplified by reverse transcriptase-polymerase chain reaction using primers binding in the 5′ and 3′ untranslated regions. Different fragments were cloned and sequenced. In wild-type RNA the common 5 domain form of ICAM-1 was identified. In RNA from ICAM-1 mutant mice only 3 smaller fragments were found. Sequencing these fragments identified 3 alternatively spliced isoforms of ICAM-1, lacking 2 or 3 extracellular domains. However, in all spliced fragments the transmembrane domain was included. Therefore, we postulate that circulating forms of ICAM-1 are generated by proteolytic cleavage of membranous ICAM-1. The data indicate that the expression of membranous ICAM-1 and the appearance of circulating forms in serum are independently regulated mechanisms.

scholarly journals High-mannose intercellular adhesion molecule-1 enhances CD16+ monocyte adhesion to the endothelium

2019 ◽  
Vol 317 (5) ◽  
pp. H1028-H1038 ◽  
Author(s):  
Kellie Regal-McDonald ◽  
Brittney Xu ◽  
Jarrod W. Barnes ◽  
Rakesh P. Patel
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Proximity Ligation Assay ◽  
Dependent Manner ◽  
Monocyte Adhesion ◽  
Monocyte Subsets ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
High Mannose

Human monocytes have been classified into three distinct groups, classical (anti-inflammatory; CD14+/CD16−), nonclassical (patrolling; CD14+/CD16++), and intermediate (proinflammatory; CD14++/CD16+). Adhesion of nonclassical/intermediate monocytes with the endothelium is important for innate immunity, and also vascular inflammatory disease. However, there is an incomplete understanding of the mechanisms that regulate CD16+ versus CD16− monocyte adhesion to the inflamed endothelium. Here, we tested the hypothesis that a high-mannose (HM) N-glycoform of intercellular adhesion molecule-1 (ICAM-1) on the endothelium mediates the selective recruitment of CD16+ monocytes. Using TNF-α treatment of human umbilical vein endothelial cells (HUVECs), and using proximity ligation assay for detecting proximity of specific N-glycans and ICAM-1, we show that TNF-α induces HM-ICAM-1 formation on the endothelial surface in a time-dependent manner. We next measured CD16− or CD16+ monocyte rolling and adhesion to TNF-α-treated HUVECs in which HM- or hybrid ICAM-1 N-glycoforms were generated using the α-mannosidase class I and II inhibitors, kifunensine and swainsonine, respectively. Expression of HM-ICAM-1 selectively enhanced CD16+ monocyte adhesion under flow with no effect on CD16− monocytes noted. CD16+ monocyte adhesion was abrogated by blocking either HM epitopes or ICAM-1. A critical role for HM-ICAM-1 in mediating CD16+ monocyte rolling and adhesion was confirmed using COS-1 cells engineered to express HM or complex ICAM-1 N-glycoforms. These data suggest that HM-ICAM-1 selectively recruits nonclassical/intermediate CD16+ monocytes to the activated endothelium. NEW & NOTEWORTHY Monocyte subsets have been associated with cardiovascular disease, yet it is unknown how different subsets are recruited to the endothelium. This study demonstrates the formation of distinct ICAM-1 N-glycoforms in the activated endothelium and reveals a key role for high mannose ICAM-1 in mediating proinflammatory CD16+ monocyte adhesion. Presented data identify roles for endothelial N-glycans in recruiting specific monocyte subsets during inflammation.

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