34 research outputs found
Endothelin-1 Stimulates Monocytes in vitro to Release Chemotactic Activity Identified as Interleukin-8 and Monocyte Chemotactic Protein-1
In the present study we examined whether endothelin-1 stimulation of
human monocytes causes release of chemotactic factors. It was found
that monocytes released neutrophil- and monocyte-chemotactic
activity in a dose- and time-dependent manner in response to ET-1.
ET-1 did not show any chemotactic activity by itself. NCA was
detected in monocyte supernatants in response to ET-1
(0.01β100 nM) after 1, 4, 8 and 24 h stimulation. MCA was
detected only after 24 h stimulation with ET-1 (0.1β100 nM).
Preincubation of the monocyte cultures with the lipoxygenase
inhibitors nordihydroguaiaretic acid (10β4 M) or
diethylcarbamazine (10β9 M) completely abolished
the appearance of NCA and MCA. NCA was neutralized by >
75% using a polyclonal antibody against human interleuktn-8.
The ET-1 induced release of IL-8 was confirmed by IL-8 ELISA. A
monoclonal antibody against human monocyte chemotactic protein-1
neutralized MCA by > 80%. It is concluded that ET-1
stimulation of monocytes in vitro causes release of
neutrophil- and monocyte-chemotactic activity identified as IL-8 and
MCP-I respectively. An intact lipoxygenase pathway is crucial for
this effect of ET-1 to occur
Endothelin-1 stimulates human monocytes in vitro to release TNF-Ξ± , IL-1Ξ² and IL-6
Increased plasma- and tissue levels of endothelin-1 (ET-1) during inflammatory diseases, have suggested a role of ET-1 in the pathophysiology of inflammatory reactions. The authors have studied the effect of ET-1 on cytokine release from monocytes and monocyte-derived macrophages. ET-1 increased secretion of TNF-Ξ±, IL-1Ξ² and IL-6 in a dose- and time-dependent manner. Optimal ET-1 concentration ranged from 0.01 to 1 nM. The maximal response was a 200 to 400% increase in cytokine release. A time-course study revealed that the pattern of cytokines induced by ET-1 was different in monocytes and macrophages, although an early increase in TNF-Ξ± was observed in both monocyte and macrophage supernatants. In conclusion, ET-1 stimulates monocytes and macrophages to release cytokines thereby demonstrating a potential role for ET-1 in regulation of inflammatory responses
New Factorization Relations for Non-Linear Sigma Model Amplitudes
We obtain novel factorization identities for non-linear sigma model
amplitudes using a new integrand in the CHY double-cover prescription. We find
that it is possible write very compact relations using only longitudinal
degrees of freedom. We discuss implications for on-shell recursion.Comment: 6 pages, no figures, version to appear in PR
Multicenter prospective observational study on safety and efficacy of regional citrate anticoagulation in CVVHD in the presence of liver failure: the Liver Citrate Anticoagulation Threshold Study (L-CAT)
Methods for Analysis of Matrix Metalloproteinase Regulation of Neutrophil-Endothelial Cell Adhesion
Recent evidence indicates novel role for matrix metalloproteinases (MMPs), in particular gelatinase A (MMP-2), in the regulation of vascular biology that are unrelated to their well-known proteolytic breakdown of matrix proteins. We have previously reported that MMP-2 can modulate vascular reactivity by cleavage of the Gly32-Leu33 bound in big endothelin-1 (ET-1) yielding a novel vasoactive peptide ET-1[1-32]. These studies were conducted to investigate whether gelatinolytic MMPs could affect neutrophil-endothelial cell attachment. ET-1[1-32] produced by MMP-2 up-regulated CD11b/CD18 expression on human neutrophils, thereby promoted their adhesion to cultured endothelial cells. ET-1[1-32] evoked release of gelatinase B (MMP-9), which in turn cleaved big ET-1 to yield ET-1[1-32], thus revealing a self-amplifying loop for ET-1[1-32] generation. ET-1[1-32] was rather resistant to cleavage by neutrophil proteases and further metabolism of ET-1[1-32] was not a prerequisite for its biological actions on neutrophils. The neutrophil responses to ET-1[1-32] were mediated via activation of ET(A)receptors through activation of the Ras/Raf-1/MEK/ERK signaling pathway. These results suggest a novel role for gelatinase A and B in the regulation of neutrophil functions and their interactions with endothelial cells. Here we describe the methods in detail as they relate to our previously published work
Islet Endothelial Activation and Oxidative Stress Gene Expression Is Reduced by IL-1Ra Treatment in the Type 2 Diabetic GK Rat
Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra)