Cytokine profiles of cultured microvascular endothelial cells from the human intestine

Nilsen, Ellen M.; Johansen, Finn–Eirik; Jahnsen, Frode L.; Lundin, Knut E.A.; Scholz, Tim; Brandtzæg, Per; Haraldsen, Guttorm

doi:10.1136/gut.42.5.635

Cited by 150 publications

(88 citation statements)

References 44 publications

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“…It is well known that ICAM-1 and VCAM-1 are markedly upregulated on endothelial cells by the proinflammatory cytokines TNF-␣ and IL-1␤, respectively (30,31), and that HUVEC and microvascular endothelial cells are able to secrete a variety of cytokines (32). Therefore, we hypothesized that RSV-induced expression of ICAM-1 and VCAM-1 is partly mediated by an autocrine mechanism as it was reported for A549 epithelial cells (33).…”

Section: Rsv-induced Expression Of Icam-1 and Vcam-1 Is Not Mediated mentioning

confidence: 93%

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

Arnold

König

2005

The Journal of Immunology

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Respiratory syncytial virus (RSV) is worldwide the most frequent cause of bronchiolitis and pneumonia in infants requiring hospitalization. In the present study, we supply evidence that human lung microvascular endothelial cells, human pulmonary lung aorta endothelial cells, and HUVEC are target cells for productive RSV infection. All three RSV-infected endothelial cell types showed an enhanced cell surface expression of ICAM-1 (CD54), which increased in a time- and RSV-dose-dependent manner. By using noninfectious RSV particles we verified that replication of RSV is a prerequisite for the increase of ICAM-1 cell surface expression. The up-regulated ICAM-1 expression pattern correlated with an increased cellular ICAM-1 mRNA amount. In contrast to ICAM-1, a de novo expression of VCAM-1 (CD106) was only observed on RSV-infected HUVEC. Neither P-selectin (CD62P) nor E-selectin (CD62E) was up-regulated by RSV on human endothelial cells. Additional experiments performed with neutralizing Abs specific for IL-1α, IL-1β, IL-6, and TNF-α, respectively, excluded an autocrine mechanism responsible for the observed ICAM-1 up-regulation. The virus-induced ICAM-1 up-regulation was dependent on protein kinase C and A, PI3K, and p38 MAPK activity. Adhesion experiments using polymorphonuclear neutrophil granulocytes (PMN) verified an increased ICAM-1-dependent adhesion rate of PMN cocultured with RSV-infected endothelial cells. Furthermore, the increased adhesiveness resulted in an enhanced transmigration rate of PMN. Our in vitro data suggest that human lung endothelial cells are target cells for RSV infection and that ICAM-1 up-regulated on RSV-infected endothelial cells might contribute to the enhanced accumulation of PMN into the bronchoalveolar space.

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Section: Rsv-induced Expression Of Icam-1 and Vcam-1 Is Not Mediated mentioning

confidence: 93%

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

Arnold

König

2005

The Journal of Immunology

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“…To address whether the tPA organelle might represent a common compartment for inflammatory molecules in ECs exposed to proinflammatory cytokines, we determined the subcellular localization of IL-6, whose endogenous levels are also up-regulated by IL-1 [27][28][29] (and supplemental Figure 1Aii). After IL-1␤ treatment, a large increase in IL-6-specific immunoreactivity was seen in the Golgi region, small puncta, and numerous WPBs (supplemental Figure 4B-C).…”

Section: Il-6 Is Present In Both the Tpa Organelle And Wpbs In Il-1␤-mentioning

confidence: 99%

A revised model for the secretion of tPA and cytokines from cultured endothelial cells

Knipe

Meli

Hewlett

et al. 2010

Blood

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Endothelial cells are reported to contain several distinct populations of regulated secretory organelles, including Weibel-Palade bodies (WPBs), the tissue plasminogen activator (tPA) organelle, and the type-2 chemokine-containing organelle. We show that the tPA and type-2 organelles in human endothelial cells represent a single compartment primarily responsible for unstimulated secretion of tPA or, in cells exposed to interleukin-1␤ (IL-1␤), the cytokines IL-8, IL-6, monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-␣ (GRO-␣). This compartment was distinct from WPBs in that it lacked detectable von Willebrand factor, P-selectin, Rab27a, or CD63 immunoreactivity, displayed no time-dependent decrease in intragranule pH, underwent detectable unstimulated exocytosis, and was very poorly responsive to Ca 2؉ -elevating secretagogues. WPBs could also contain tPA, and in IL-1␤-treated cells, IL-8, IL-6, MCP-1, and GRO-␣, and were the primary source for histamine or ionomycin-stimulated secretion of these molecules. However, analysis of the storage efficiency of cytokines and tPA revealed that all were very poorly stored compared with von Willebrand factor. The nonmammalian, nonsecretory protein EGFP, when expressed in the secretory pathway, also entered WPBs and had a storage efficiency similar to tPA and the cytokines tested. Based on these data, we proposed a revised model for storage and secretion of cytokines and tPA. (Blood. 2010;116(12):2183-2191) IntroductionSeveral studies suggest that endothelial cells (ECs) possess several distinct populations of regulated secretory organelles (RSOs) in which different subsets of bioactive peptides and proteins are stored, trafficked, and rapidly secreted in response to physiologic stimuli. These include (1) Weibel-Palade bodies (WPBs) whose major cargo protein is von Willebrand factor (VWF) 1 ; (2) a small punctate organelle, morphologically distinct from WPBs, lacking endogenous VWF immunoreactivity but containing the anticoagulant protein tissue plasminogen activator (tPA; the tPA organelle) 2-4 ; and (3) a small punctate organelle, reported to specifically contain the small chemotactic cytokines growthregulated oncogene-␣ (GRO-␣) and monocyte chemoattractant protein 1 (MCP-1) and termed the type-2 granule. 5 The presence of distinct populations of RSOs within the same cell is not uncommon 6-8 and may allow the stimulated release of diverse bioactive molecules to be differentially controlled. If distinct populations of RSOs do exist in ECs, then a careful examination of their properties would provide insights into how trafficking and secretion of specific groups of bioactive molecules are regulated.WPBs are the best characterized RSO of ECs. After their formation at the trans-Golgi network (TGN), WPBs accumulate in the cytoplasm and can remain within the cell for long periods of time (1-2 days). 9,10 By these criteria, we define WPBs as true storage organelles. Under resting conditions, WPBs undergo a very slow process of basal exocytosis, 10 undete...

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“…The functional role of endothelial TLR5 was demonstrated by induction of leukocyte adhesion and transmigration, pointing to a previously unrecognized role of endothelial TLR5 in the innate immunity. 31 Nielsen and colleagues, 32 who studied the cytokine expression profile of HIMECs by exposing cultured cells to recombinant cytokines and LPS, provide additional evidence for the involvement of microcirculation in innate immunity. Their work indicates that intestinal microvascular endothelium can constitutively produce several cytokines, which are up-regulated after stimulation with cytokines or LPS, suggesting that microvasculature may contribute to the cytokine network of the gut mucosa with the ability to respond to locally generated cytokines and to produce potent inflammatory mediators.…”

mentioning

confidence: 99%

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Deban

Correale

Vetrano

et al. 2008

The American Journal of Pathology

122

100

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The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.

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Cytokine profiles of cultured microvascular endothelial cells from the human intestine

Cited by 150 publications

References 44 publications

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

A revised model for the secretion of tPA and cytokines from cultured endothelial cells

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

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