Cytokine Regulation of Endothelial Cell Function

Mantovani, Alberto; Allavena, Paola; Vecchi, Annunciata; Dejana, Elisabetta; Sozzani, Silvano; Introna, Martino

doi:10.1007/978-1-4899-0133-0_9

Cited by 99 publications

(121 citation statements)

References 206 publications

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“…tory cytokines in RA. Both IL-1 (13)(14)(15) and TNF␣ (16,17), 2 master cytokines that play a significant role in RA (3), are known to promote angiogenesis. Given this intense interest in anticytokine biologics, our experiments provide important new information regarding the ability of such novel therapeutic molecules to regulate neovascularization in the arthritic joint.…”

Section: Discussionmentioning

confidence: 99%

“…IL-1 (13)(14)(15) and TNF␣ (16)(17)(18)(19) both also have been implicated as angiogenic factors. This finding is provocative because angiogenesis is a critical component in the initiation and maintenance of pannus, the aggressive fibrovascular extension of synovial tissue that is responsible for the extensive bone and cartilage damage in RA (20) and experimental models of arthritis (21).…”

mentioning

confidence: 99%

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Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Coxon¹,

Bolon²,

Estrada³

et al. 2002

Arthritis & Rheumatism

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Objective. To assess the capacities of the cytokine inhibitors interleukin-1 receptor antagonist (IL-1Ra; anakinra) and PEGylated soluble tumor necrosis factor receptor I (PEG sTNFRI; pegsunercept) to suppress neovascularization.Methods. A corneal angiogenesis assay was performed by implanting nylon discs impregnated with an angiogenic stimulator (basic fibroblast growth factor or vascular endothelial growth factor) into one cornea of female Sprague-Dawley rats. Animals were treated with IL-1Ra or PEG sTNFRI for 7 days, after which new vessels were quantified. In a parallel study, male Lewis rats with mycobacteria-induced adjuvant-induced arthritis were treated with IL-1Ra or PEG sTNFRI for 7 days beginning at disease onset, after which scores for inflammation and bone erosion as well as capillary counts were acquired from sections of arthritic hind paws.Results. Treatment with IL-1Ra yielded a dosedependent reduction in growth factor-induced corneal angiogenesis, while PEG sTNFRI did not. IL-1Ra, but not PEG sTNFRI, significantly reduced the number of capillaries in arthritic paws, even though both anticytokines reduced inflammation and bone erosion to a similar degree.Conclusion. These data support a major role for IL-1, but not TNF␣, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL-1 inhibitors, but not anti-TNF agents, is the suppression of the angiogenic component of pannus.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Coxon¹,

Bolon²,

Estrada³

et al. 2002

Arthritis & Rheumatism

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“…Endothelial cells have the potential to synthesize interleukines, colony-stimulating factors and chemokines (Bierhaus et al, 2000). Upon stimulation by LPS, tumor necrosis factor-a (TNF-a) or IL-1, endothelial cells respond with production and release of these cytokines and growth factors (Pober, 1987;Mantovani et al, 1992;Krishnaswamy et al, 1999). Because endothelial cells also respond to some of the cytokines and growth factors secreted, paracrine, and autocrine stimuli further promote the proinflammatory endothelial response.…”

Section: Endothelial Cell Responses To Cytokinesmentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

599

429

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Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

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“…IL-1 and TNF-␣ are important mediators leading to increased expression of adhesion molecules E-selectin, VCAM-1, and ICAM-1 as well as expression of soluble proinflammatory cytokines, e.g., MCP-1, M-CSF, IL-6, and IL-8, by the endothelium (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The subsequent recruitment of leukocytes to inflamed tissue requires their tethering and rolling as well as rapid activation of integrin-dependent arrest on the target endothelium as a checkpoint for diapedesis to the extravascular tissue (17,18).…”

mentioning

confidence: 99%

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness

Richter¹,

Bistrian

Escher³

et al. 2005

The Journal of Immunology

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Monocyte infiltration into inflammatory sites is generally preceded by neutrophils. We show here that neutrophils may support this process by activation of CCL15, a human chemokine circulating in blood plasma. Neutrophils were found to release CCL15 proteolytic activity in the course of hemofiltration of blood from renal insufficiency patients. Processing of CCL15 immunoreactivity (IR) in the pericellular space is suggested by a lack of proteolytic activity in blood and blood filtrate, but a shift of the retention time (tR) of CCL15-IR, detected by chromatographic separation of CCL15-IR in blood and hemofiltrate. CCL15 molecules with N-terminal deletions of 23 (Δ23) and 26 (Δ26) aa were identified as main proteolytic products in hemofiltrate. Neutrophil cathepsin G was identified as the principal protease to produce Δ23 and Δ26 CCL15. Also, elastase displays CCL15 proteolytic activity and produces a Δ21 isoform. Compared with full-length CCL15, Δ23 and Δ26 isoforms displayed a significantly increased potency to induce calcium fluxes and chemotactic activity on monocytes and to induce adhesiveness of mononuclear cells to fibronectin. Thus, our findings indicate that activation of monocytes by neutrophils is at least in part induced by quantum proteolytic processing of circulating or endothelium-bound CCL15 by neutrophil cathepsin G.

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Cytokine Regulation of Endothelial Cell Function

Cited by 99 publications

References 206 publications

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Endothelial cell functions

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness

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