scholarly journals Expression and Function of the Homeostatic Molecule Del-1 in Endothelial Cells and the Periodontal Tissue

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jieun Shin ◽  
Kavita B. Hosur ◽  
Kalyani Pyaram ◽  
Ravi Jotwani ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Inflammatory Cell ◽  
Leukocyte Adhesion ◽  
Neutrophil Infiltration ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression ◽  
Reciprocal Regulation ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM)-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin). Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3) by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.

scholarly journals Gingipains of Porphyromonas gingivalis Modulate Leukocyte Adhesion Molecule Expression Induced in Human Endothelial Cells by Ligation of CD99

2006 ◽  
Vol 74 (3) ◽  
pp. 1661-1672 ◽  
Author(s):  
Peter L. W. Yun ◽  
Arthur A. DeCarlo ◽  
Neil Hunter
Keyword(s):  
Endothelial Cells ◽  
Porphyromonas Gingivalis ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression ◽  
Leukocyte Adhesion Molecule

ABSTRACT Porphyromonas gingivalis has been implicated as a key etiologic agent in the pathogenesis of destructive chronic periodontitis. Among virulence factors of this organism are cysteine proteinases, or gingipains, that have the capacity to modulate host inflammatory defenses. Intercellular adhesion molecule expression by vascular endothelium represents a crucial process for leukocyte transendothelial migration into inflamed tissue. Ligation of CD99 on endothelial cells was shown to induce expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and major histocompatibility complex class II molecules and to increase adhesion of leukocytes. CD99 ligation was also found to induce nuclear translocation of NF-κB. These results indicate that endothelial cell activation by CD99 ligation may lead to the up-regulation of adhesion molecule expression via NF-κB activation. However, pretreatment of endothelial cells with gingipains caused a dose-dependent reduction of adhesion molecule expression and leukocyte adhesion induced by ligation of CD99 on endothelial cells. The data provide evidence that the gingipains can reduce the functional expression of CD99 on endothelial cells, leading indirectly to the disruption of adhesion molecule expression and of leukocyte recruitment to inflammatory foci.

Deficiency of endothelial CD40 induces a stable plaque phenotype and limits inflammatory cell recruitment to atherosclerotic lesions in mice

2021 ◽  
Author(s):  
Mark Colin Gissler ◽  
Philipp Scherrer ◽  
Nathaly Anto Michel ◽  
Jan Pennig ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Cell ◽  
Leukocyte Adhesion ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Intercellular Adhesion Molecule ◽  
Atherosclerotic Plaques ◽  
Chow Diet ◽  
Stable Plaque ◽  
Plaque Phenotype

Objectives: The co-stimulatory CD40L-CD40 dyad exerts a critical role in atherosclerosis by modulating leukocyte accumulation into developing atherosclerotic plaques. The requirement for cell-type specific expression of both molecules, however, remains elusive. Here, we evaluate the contribution of CD40 expressed on endothelial cells (ECs) in a mouse model of atherosclerosis. Approach & Results: Atherosclerotic plaques of Apolipoprotein E deficient (Apoe-/-) mice and humans displayed increased expression of CD40 on ECs compared to controls. To interrogate the role of CD40 on ECs in atherosclerosis, we induced EC-specific (BmxCreERT2-driven) deficiency of CD40 in Apoe-/- mice. After feeding a chow diet for 25 weeks, EC-specific deletion of CD40 (iEC-CD40) ameliorated plaque lipid deposition and lesional macrophage accumulation but increased intimal smooth muscle cell and collagen content, while atherosclerotic lesion size did not change. Leukocyte adhesion to the vessel wall was impaired in iEC-CD40-deficient mice as demonstrated by intravital microscopy. In accord, expression of vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the vascular endothelium declined after deletion of CD40. In vitro, antibody-mediated inhibition of human endothelial CD40 significantly abated monocyte adhesion on ECs. Conclusions: Endothelial deficiency of CD40 in mice promotes structural features associated with a stable plaque phenotype in humans and decreases leukocyte adhesion. These results suggest that endothelial-expressed CD40 contributes to inflammatory cell migration and consecutive plaque formation in atherogenesis.

Effect of hyperoxia on adhesion molecule expression in human endothelial cells and neutrophils

1997 ◽  
Vol 272 (3) ◽  
pp. L418-L425 ◽  
Author(s):  
Y. Suzuki ◽  
T. Aoki ◽  
O. Takeuchi ◽  
K. Nishio ◽  
K. Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Oxygen Toxicity ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression ◽  
Neutrophil Accumulation ◽  
Protein Kinase C Inhibitor ◽  
Human Pulmonary Artery ◽  
Umbilical Vein Endothelial Cells

To investigate the pathogenesis of pulmonary oxygen toxicity, we examined the effect of hyperoxia on adhesion molecule expression in cultured human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Endothelial cell monolayers were exposed to either hyperoxic (90% O(2)-5% CO(2)) or normoxic (21% O(2)-5% CO(2)) conditions for various periods. The level of intercellular adhesion molecule (ICAM)-1 expression had increased in hyperoxia-exposed HPAEC and HUVEC at 48 h (194 +/- 38 and 233 +/- 56%, respectively; P < 0.001) and at 72 h (200 +/- 43 and 223 +/- 52%, respectively; P < 0.001) compared with normoxic conditions. These hyperoxia-induced ICAM-1 expressions were dose dependently attenuated by a protein kinase C inhibitor (H-7). In contrast, the levels of P-selectin and E-selectin expression in HPAEC and HUVEC were unchanged. The levels of ICAM-1 mRNA and the numbers of adherent neutrophils were increased in HPAEC and HUVEC at 48 and 72 h of hyperoxia. On the other hand, hyperoxia caused neutrophil H(2)O(2) production without affecting the level of CD11/CD18 expression. These results suggest that increased ICAM-1 expression in endothelial cells plays an important role in neutrophil accumulation during hyperoxia.

scholarly journals The Role of PPARs in the Endothelium: Implications for Cancer Therapy

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
David Bishop-Bailey ◽  
Karen E. Swales
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Platelet Activation ◽  
Inflammatory Cell ◽  
Cell Layer ◽  
Cell Recruitment ◽  
Blood Vessel Formation ◽  
Endothelial Cell Layer ◽  
Inflammatory Cell Recruitment

The growth and metastasis of cancers intimately involve the vasculature and in particular the endothelial cell layer. Tumours require new blood vessel formation via angiogenesis to support growth. In addition, inflammation, coagulation, and platelet activation are common signals in the growth and metastasis of tumour cells. The endothelium plays a central role in the homeostatic control of inflammatory cell recruitment, regulating platelet activation and coagulation pathways. PPAR, -/, and - are all expressed in endothelial cells. This review will discuss the roles of PPARs in endothelial cells in relation to angiogenesis, inflammation, coagulation, and platelet control pathways. In particular, we will discuss the recent evidence that supports the hypothesis that PPAR and PPAR are antiangiogenic receptors, while PPAR/ is proangiogenic.

scholarly journals TRAF5 Deficiency Accelerates Atherogenesis in Mice by Increasing Inflammatory Cell Recruitment and Foam Cell Formation

2010 ◽  
Vol 107 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Anna Missiou ◽  
Philipp Rudolf ◽  
Peter Stachon ◽  
Dennis Wolf ◽  
Nerea Varo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cell ◽  
Foam Cell ◽  
Interleukin 1 ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
High Cholesterol Diet ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Rationale: Tumor necrosis factor receptor–associated factors (TRAFs) are cytoplasmic adaptor proteins for the TNF/interleukin-1/Toll-like receptor superfamily. Ligands of this family comprise multiple important cytokines such as TNFα, CD40L, and interleukin-1β that promote chronic inflammatory diseases such as atherosclerosis. We recently reported overexpression of TRAF5 in murine and human atheromata and that TRAF5 promotes inflammatory functions of cultured endothelial cells and macrophages. Objective: This study tested the hypothesis that TRAF5 modulates atherogenesis in vivo. Methods and Results: Surprisingly, TRAF5 −/− /LDLR −/− mice consuming a high-cholesterol diet for 18 weeks developed significantly larger atherosclerotic lesions than did TRAF5 +/+ /LDLR −/− controls. Plaques of TRAF5-deficient animals contained more lipids and macrophages, whereas smooth muscle cells and collagen remained unchanged. Deficiency of TRAF5 in endothelial cells or in leukocytes enhanced adhesion of inflammatory cells to the endothelium in dynamic adhesion assays in vitro and in murine vessels imaged by intravital microscopy in vivo. TRAF5 deficiency also increased expression of adhesion molecules and chemokines and potentiated macrophage lipid uptake and foam cell formation. These findings coincided with increased activation of JNK and appeared to be independent of TRAF2. Finally, patients with stable or acute coronary heart disease had significantly lower amounts of TRAF5 mRNA in blood compared with healthy controls. Conclusions: Unexpectedly, TRAF5 deficiency accelerates atherogenesis in mice, an effect likely mediated by increased inflammatory cell recruitment to the vessel wall and enhanced foam cell formation.

scholarly journals Infection of Endothelial Cells with Trypanosoma cruziActivates NF-κB and Induces Vascular Adhesion Molecule Expression

1999 ◽  
Vol 67 (10) ◽  
pp. 5434-5440 ◽  
Author(s):  
Huan Huang ◽  
Tina M. Calderon ◽  
Joan W. Berman ◽  
Vicki L. Braunstein ◽  
Louis M. Weiss ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Response ◽  
Adhesion Molecule ◽  
Transcriptional Activation ◽  
Consensus Sequence ◽  
Intercellular Adhesion Molecule ◽  
Immunocytochemical Staining ◽  
Adhesion Molecule Expression ◽  
Nuclear Extracts ◽  
Vascular Adhesion

ABSTRACT Transcriptional activation of vascular adhesion molecule expression, a major component of an inflammatory response, is regulated, in part, by the nuclear factor-κB/Rel (NF-κB) family of transcription factors. We therefore determined whetherTrypanosoma cruzi infection of endothelial cells resulted in the activation of NF-κB and the induction or increased expression of adhesion molecules. Human umbilical vein endothelial cells (HUVEC) were infected with trypomastigotes of the Tulahuen strain of T. cruzi. Electrophoretic mobility shift assays with an NF-κB-specific oligonucleotide and nuclear extracts from T. cruzi-infected HUVEC (6 to 48 h postinfection) detected two major shifted complexes. Pretreatment with 50× cold NF-κB consensus sequence abolished both gel-shifted complexes while excess SP-1 consensus sequence had no effect. These data indicate that nuclear extracts from T. cruzi-infected HUVEC specifically bound to the NF-κB consensus DNA sequence. Supershift analysis revealed that the gel-shifted complexes were comprised of p65 (RelA) and p50 (NF-κB1). Northern blot analyses demonstrated both the induction of vascular cell adhesion molecule 1 and E-selectin and the upregulation of intercellular adhesion molecule 1 mRNA in HUVEC infected withT. cruzi. Immunocytochemical staining confirmed adhesion molecule expression in response to T. cruzi infection. These findings are consistent with the hypothesis that the activation of the NF-κB pathway in endothelial cells associated with T. cruzi infection may be an important factor in the inflammatory response and subsequent vascular injury and endothelial dysfunction that lead to chronic cardiomyopathy.

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