IL-8 release and neutrophil activation byClostridium difficiletoxin-exposed human monocytes

1997 ◽  
Vol 273 (6) ◽  
pp. G1333-G1340 ◽  
Author(s):  
Joanne K. Linevsky ◽  
Charalabos Pothoulakis ◽  
Sarah Keates ◽  
Michel Warny ◽  
Andrew C. Keates ◽  
...  
Keyword(s):  
Neutrophil Migration ◽  
Neutrophil Infiltration ◽  
Neutrophil Activation ◽  
Conditioned Media ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Toxin B ◽  
Low Concentrations ◽  
Neutrophil Extravasation

Neutrophil infiltration is central to the pathogenesis of Clostridium difficiletoxin A-induced enterocolitis. This study examines whether monocyte activation by C. difficile toxins is instrumental in initiating neutrophil activation and recruitment. Human monocytes were exposed to low concentrations of highly purified C. difficile toxins, and the conditioned media were harvested for cytokine and functional assays. Monocytes exposed to C. difficiletoxin A (10−10M) or toxin B (10−12M) released 100 and 20 times basal levels, respectively, of the neutrophil chemoattractant interleukin-8 (IL-8). Reverse transcriptase-polymerase chain reaction demonstrated a marked increase in IL-8 mRNA expression by monocytes 3 h after toxin exposure. Conditioned media from toxin A- and toxin B-treated monocytes stimulated neutrophil migration (324 and 245% of control, respectively). This effect was completely blocked by IL-8 antiserum. These media also upregulated neutrophil CD11b/CD18 and endothelial cell intercellular adhesion molecule-1 expression. C. difficile toxins, at low concentrations, potently activate monocytes to release factors, including IL-8, that facilitate neutrophil extravasation and tissue infiltration. Our findings indicate a major role for toxin-mediated monocyte and macrophage activation in C. difficile colitis.

IL-8 secretion and neutrophil activation by HT-29 colonic epithelial cells

1994 ◽  
Vol 267 (6) ◽  
pp. G991-G997 ◽  
Author(s):  
C. P. Kelly ◽  
S. Keates ◽  
D. Siegenberg ◽  
J. K. Linevsky ◽  
C. Pothoulakis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Inflammation ◽  
Neutrophil Migration ◽  
Intercellular Adhesion Molecule ◽  
Northern Hybridization ◽  
Intercellular Adhesion Molecule 1 ◽  
Colonic Epithelial Cells ◽  
Neutrophil Extravasation ◽  
Cytokine Stimulation ◽  
Ht 29

This study examines the ability of HT-29 human colonic epithelial cells to stimulate neutrophil migration and adhesion. Interleukin-8 (IL-8), a potent neutrophil chemoattractant, was detected in conditioned media from both unstimulated (1.1 ng/ml) and IL-1 beta-stimulated (16.1 ng/ml) HT-29 cultures. Conditioned medium from IL-1 beta-exposed HT-29 cells stimulated neutrophil migration (395% of control, P < 0.01), and this effect was completely inhibited by anti-IL-8 antibody. HT-29 medium also induced shedding of neutrophil L-selectin and increased expression of neutrophil CD11/CD18 adhesion receptors. Coculture of HT-29 cells with human endothelial cell monolayers resulted in increased neutrophil transendothelial migration (169% of control, P < 0.01), which was blocked by both anti-IL-8 and anti-CD18 antibody. Northern hybridization analysis demonstrated increased levels of mRNA for IL-8 and intercellular adhesion molecule-1 (ICAM-1) in cytokine-treated HT-29 cells. Cytokine stimulation of HT-29 monolayers was also associated with increased neutrophil adhesion to these cells. Neutrophil-HT-29 cell adhesion was blocked by monoclonal antibodies to neutrophil CD18 or to ICAM-1 on the HT-29 cells (86% and 56% inhibition, respectively, P < 0.01 for both). These data suggest that IL-8 secretion by activated colonic epithelial cells may contribute to neutrophil extravasation and tissue infiltration in intestinal inflammation.

scholarly journals Interleukin-10 Inhibits Interferon-γ–Induced Intercellular Adhesion Molecule-1 Gene Transcription in Human Monocytes

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4461-4469 ◽  
Author(s):  
Seng Song ◽  
Hsiang Ling-Hu ◽  
Kenneth A. Roebuck ◽  
Mohammed F. Rabbi ◽  
Raymond P. Donnelly ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Gene Transcription ◽  
Adhesion Molecule ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Ifn Γ

Abstract Interleukin-10 (IL-10) is a potent monocyte regulatory cytokine that inhibits gene expression of proinflammatory mediators. In this study, we investigated the mechanism by which IL-10 downregulates expression of intercellular adhesion molecule-1 (ICAM-1) on the cell surface of normal human monocytes activated with interferon-γ (IFN-γ). IL-10 inhibition of IFN-γ–induced ICAM-1 expression was apparent as early as 3 hours and was blocked by an anti–IL-10 antibody but not by an isotype-matched control antibody. Northern blot analysis showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-γ–stimulated monocytes. IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours and remained at 24 hours. Nuclear run-on transcription assays showed that IL-10 inhibited the rate of IFN-γ–induced transcription of the ICAM-1 gene, and mRNA stability studies showed that IL-10 did not alter the half-life of IFN-γ–induced ICAM-1 message. Thus, IL-10 inhibits IFN-γ–induced ICAM-1 expression in monocytes primarily at the level of gene transcription. Activation of IFN-γ–responsive genes requires tyrosine phosphorylation of the transcriptional factor STAT-1α (signal transducer and activator of transcription-1α). However, IL-10 did not affect IFN-γ–induced tyrosine phosphorylation of STAT-1α or alter STAT-1α binding to the IFN-γ response element (IRE) in the ICAM-1 promoter. Instead, IL-10 prevented IFN-γ–induced binding activity at the NF-κB site of the tumor necrosis factor α (TNF-α)–responsive NF-κB/C-EBP composite element in the ICAM-1 promoter. These data indicate that IL-10 inhibits IFN-γ–induced transcription of the ICAM-1 gene by a regulatory mechanism that may involve NF-κB.

IL-18-Induced Expression of Intercellular Adhesion Molecule-1 in Human Monocytes: Involvement in IL-12 and IFN-γ Production in PBMC

2001 ◽  
Vol 210 (2) ◽  
pp. 106-115 ◽  
Author(s):  
Atsushi Yoshida ◽  
Hideo Kohka Takahashi ◽  
Masahiro Nishibori ◽  
Hiromi Iwagaki ◽  
Tadashi Yoshino ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Induced Expression ◽  
Ifn Γ

scholarly journals Dietary fish oil enhances adhesion molecule and interleukin-6 expression in mice with polymicrobial sepsis

2006 ◽  
Vol 96 (5) ◽  
pp. 854-860 ◽  
Author(s):  
Chun-Sen Hsu ◽  
Wan-Chun Chiu ◽  
Chiu-Li Yeh ◽  
Yu-Chen Hou ◽  
Szu-Yuan Chou ◽  
...  
Keyword(s):  
Fish Oil ◽  
Adhesion Molecule ◽  
Neutrophil Infiltration ◽  
Interferon Γ ◽  
Polymicrobial Sepsis ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Group 12 ◽  
Dietary Fish

This study investigated the effects of fish oil (FO) diet on plasma intercellular adhesion molecule 1 (ICAM-1) levels and leucocyte integrin expression in polymicrobial sepsis. Mice were randomly assigned to a control group and an FO group. The control group was fed a medium-fat diet containing soyabean oil, whereas in the FO group, 70 % of the soyabean oil was replaced by FO for 3 weeks. After that, sepsis was induced by caecal ligation and puncture (CLP) in the experimental groups and mice were killed at 0, 6, 12 and 24 h, respectively, after CLP. Results showed that compared with the control group, plasma ICAM-1 levels were higher in the FO group 6 h after CLP. Intra-lymphocyte interferon-γ expression in the FO group was lower, whereas IL-4 expression was higher than in the control group 12 and 24 h after CLP. The expression of leucocyte integrin was significantly higher in the FO group 12 and 24 h after CLP. The FO group had higher IL-6 levels at 12 h in the lungs, at 6 and 12 h in the kidneys, and at 6, 12 and 24 h in the intestines after CLP. The survival rate did not differ between the two groups after CLP. The present findings suggest that pretreatment with an FO diet enhances adhesion molecule and inflammatory cytokine expressions during sepsis, which might aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, FO diet promotes the Th2-type response and suppresses cellular immune response in polymicrobial sepsis.

Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells

2000 ◽  
Vol 279 (4) ◽  
pp. G666-G676 ◽  
Author(s):  
Vjekoslav Zaninovic ◽  
Anna S. Gukovskaya ◽  
Ilya Gukovsky ◽  
Michelle Mouria ◽  
Stephen J. Pandol
Keyword(s):  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Nuclear Factor Κb ◽  
Pancreatic Acinar Cells ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Basal Expression ◽  
Activation Of Transcription

Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone (cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was upregulated in pancreas of rats with experimental pancreatitis induced by supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar cells. Inhibitory analysis showed that activation of transcription factor nuclear factor-κB (NF-κB) was involved in ICAM-1 upregulation by cerulein, but NF-κB did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an adhesion assay, we found that neutrophils bind to isolated pancreatic acinar cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1 antibody blocked neutrophil binding to both control and cerulein-stimulated acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar cell is capable of targeting neutrophils to its surface, a process that may be important for inflammatory and cell death responses in pancreatitis and other pancreatic disorders.

scholarly journals Diminished Adhesion of Anaplasma phagocytophilum-Infected Neutrophils to Endothelial Cells Is Associated with Reduced Expression of Leukocyte Surface Selectin

2003 ◽  
Vol 71 (8) ◽  
pp. 4586-4594 ◽  
Author(s):  
Kyoung-Seong Choi ◽  
Justin Garyu ◽  
Jinho Park ◽  
J. Stephen Dumler
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Anaplasma Phagocytophilum ◽  
Opportunistic Infections ◽  
Tissue Injury ◽  
Neutrophil Activation ◽  
Intercellular Adhesion Molecule ◽  
Immunoglobulin Superfamily ◽  
Intercellular Adhesion Molecule 1 ◽  
Activation Markers

ABSTRACT Anaplasma phagocytophilum propagates within neutrophils and causes a disease marked by inflammatory tissue injury or complicated by opportunistic infections. We hypothesized that infection with A. phagocytophilum modifies the binding of neutrophils to endothelial cells and the expression of neutrophil adhesion molecules and studied these changes in vitro. Infected dimethyl sulfoxide-differentiated HL-60 cells and neutrophils showed reduced binding to cultured brain and systemic endothelial cells and lost expression of P-selectin glycoprotein ligand 1 (PSGL-1, CD162) and L-selectin (CD62L) (to 33 and 5% of control values, respectively), at a time when the levels of β2 integrin and immunoglobulin superfamily adhesion molecules and activation markers Mac-1 and intercellular adhesion molecule 1 increased (5 to 10 times that of the control). The loss of CD162 and CD62L expression was inhibited by EDTA, which suggests that neutrophil activation and sheddase cleavage occurred. The loss of selectin expression and the retained viability of the neutrophils persisted for at least 18 h with A. phagocytophilum infection, whereas Escherichia coli and Staphylococcus aureus rapidly killed neutrophils. The adhesion defect might increase the numbers of infected cells and their persistence in the blood prior to tick bites. However, decreased CD162 expression and poor endothelial cell binding may partly explain impaired host defenses, while simultaneous neutrophil activation may aggravate inflammation. These observations may help us to understand the modified biological responses, host inflammation, and immune response that occur with A. phagocytophilum infections.

Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes

1994 ◽  
Vol 24 (4) ◽  
pp. 1007-1009 ◽  
Author(s):  
Fabienne Willems ◽  
Arnaud Marchant ◽  
Jean-Pierre Delville ◽  
Catherine Gérard ◽  
Anne Delvaux ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Interleukin 10 ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Intercellular Adhesion Molecule 1

scholarly journals Porphyromonas gingivalis RgpA-Kgp Proteinase-Adhesin Complexes Penetrate Gingival Tissue and Induce Proinflammatory Cytokines or Apoptosis in a Concentration-Dependent Manner

2008 ◽  
Vol 77 (3) ◽  
pp. 1246-1261 ◽  
Author(s):  
Neil M. O'Brien-Simpson ◽  
Rishi D. Pathirana ◽  
Glenn D. Walker ◽  
Eric C. Reynolds
Keyword(s):  
Connective Tissue ◽  
Porphyromonas Gingivalis ◽  
Intercellular Adhesion Molecule ◽  
Gingival Tissue ◽  
Dependent Manner ◽  
Intercellular Adhesion Molecule 1 ◽  
Concentration Dependent Manner ◽  
Proinflammatory Mediators ◽  
Low Concentrations ◽  
High Concentrations

ABSTRACT The RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis were observed, using immunostaining, in human gingival tissue associated with periodontitis but not in healthy tissue. The staining pattern suggested a concentration gradient from the subgingival plaque into the subjacent gingival connective tissue. Intense immunostaining was observed in areas displaying gross disturbance of tissue architecture. P. gingivalis cells and the RgpA-Kgp complexes at low concentrations were shown to stimulate secretory intercellular adhesion molecule 1, interleukin-8 (IL-8), IL-6, and macrophage chemoattractant protein secretion from cultured human epithelial (KB) and fibroblast (MRC-5) cells. However, at high concentrations a reduction in the level of these mediators was observed. In contrast, macrophage inflammatory protein 1α and IL-1α were stimulated only at high P. gingivalis cell concentrations. P. gingivalis cells and the RgpA-Kgp complexes were shown to induce apoptosis in KB and MRC-5 cells in a time- and dose-dependent manner. These data suggest that the RgpA-Kgp complexes penetrate the gingival connective tissue; at low concentrations distal from the plaque the complexes stimulate the secretion of proinflammatory mediators, while at high concentrations proximal to the plaque they induce apoptosis and attenuate the secretion of proinflammatory mediators.

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