Effects of glucocorticoids on activation of c-jun N-terminal, extracellular signal-regulated, and p38 MAP kinases in human pulmonary endothelial cells††Abbreviations: AP-1, activator protein-1; Dex, dexamethasone; ERK, extracellular signal-regulated kinases; GCS, glucocorticosteroids; GR, glucocorticoid receptors; H2O2, hydrogen peroxide; HMVEC-L, human microvascular endothelial cells from lung; IL-1β, interleukin-1β; JNK, c-jun N-terminal kinases; MAPK, mitogen-activated protein kinases; Test testosterone; and TNF-α, tumour necrosis factor-α.

2001 ◽  
Vol 62 (12) ◽  
pp. 1719-1724 ◽  
Author(s):  
Girolamo Pelaia ◽  
Giovanni Cuda ◽  
Alessandro Vatrella ◽  
Rosa Daniela Grembiale ◽  
Giovanbattista De Sarro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Map Kinases ◽  
Glucocorticoid Receptors ◽  
Activator Protein 1 ◽  
Pulmonary Endothelial Cells ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept

2016 ◽  
Vol 9 ◽  
pp. CMAMD.S34424 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Koei Oh ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Map Kinases ◽  
Histological Changes ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Hematoxylin And Eosin ◽  
Factor Α ◽  
Necrosis Factor ◽  
And Cartilage

The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

scholarly journals Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors

2021 ◽  
Author(s):  
Hanna Galganska ◽  
Wieslawa Jarmuszkiewicz ◽  
Lukasz Galganski
Keyword(s):  
Carbon Dioxide ◽  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Proinflammatory Responses ◽  
Factor Α ◽  
Preclinical And Clinical Studies

AbstractMitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe coronavirus disease 2019 (COVID-19). In this work, we demonstrate that human MAPKs, i.e. extracellular signal-regulated kinases 1 and 2 (ERK1/2), are CO2 sensors and CO2 is an efficient anti-inflammatory compound that exerts its effects through inactivating ERK1/2 in cultured endothelial cells when the CO2 concentration is elevated. CO2 is a potent inhibitor of cellular proinflammatory responses caused by H2O2 or the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. ERK1/2 activated by the combined action of RBD and cytokines crucial for the development of severe COVID-19, i.e. interferon-gamma (IFNγ) and tumour necrosis factor-α (TNFα), are more effectively inactivated by CO2 than by dexamethasone or acetylsalicylic acid in human bronchial epithelial cells. Previously, many preclinical and clinical studies showed that the transient application of 5–8% CO2 is safe and effective in the treatment of many diseases. Therefore, our research indicates that CO2 may be used for the treatment of COVID-19 as well as the modification of hundreds of cellular pathways.

scholarly journals Delivering Minocycline into Brain Endothelial Cells with Liposome-Based Technology

2012 ◽  
Vol 32 (6) ◽  
pp. 983-988 ◽  
Author(s):  
Changhong Xing ◽  
Tatyana Levchenko ◽  
Shuzhen Guo ◽  
Monique Stins ◽  
Vladimir P Torchilin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis ◽  
Proof Of Concept ◽  
Brain Endothelial Cells ◽  
Cerebral Endothelium ◽  
Low Concentrations ◽  
Tnf Α ◽  
Factor Α ◽  
Very High ◽  
Necrosis Factor

Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis factor α (TNF α)-induced MMP-9 release from endothelial cells. But low concentrations of minocycline-loaded liposomes significantly reduced TNF α-induced MMP-9 release. This study provides proof-of-concept that liposomes may be used to deliver lower levels of minocycline for targeting MMPs in cerebral endothelium.

In VitroProtective Effects of Two Extracts from Bergamot Peels on Human Endothelial Cells Exposed to Tumor Necrosis Factor-α (TNF-α)

2010 ◽  
Vol 58 (14) ◽  
pp. 8430-8436 ◽  
Author(s):  
Domenico Trombetta ◽  
Francesco Cimino ◽  
Mariateresa Cristani ◽  
Giuseppina Mandalari ◽  
Antonella Saija ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Endothelial Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

2015 ◽  
Vol 59 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Xinran Li ◽  
Renli Jiang ◽  
Guanying Wang ◽  
Yue Li ◽  
Xiaojing Fan ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Plasma Concentrations ◽  
Clinical Signs ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Developmental Phase ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Necrosis Factor

Abstract The study was conducted on 24 Mongolian horses, with oligofructose-induced equine laminitis (10 g/kg b.w.). The objective of the study was to investigate the relationships among matrix metalloproteinase 2 (MMP-2), P38 mitogen-activated protein kinases (P38 MAPK), tissue inhibitor of metalloproteinase 2 (TIMP-2), lipopolysaccharides (LPS), and tumour necrosis factor-α (TNF-α) during acute developmental phase of laminitis, and to determine whether there are any characteristic tendencies. Moreover, plasma concentrations of LPS and TNF-α were measured in order to determine the time of leukocytes’ activation. Eleven of the 12 horses showed clinical signs of laminitis. The contents of MMP-2 and P38 MAPK increased significantly from 8 h to 64 h, and the content of TIMP-2 decreased significantly at the same time. Plasma LPS concentrations increased significantly between 8 h and 20 h and reached a peak of 0.024 ± 0.009 EU/mL (equivalent to 3.04 ± 1.19 pg/mL) at 12 h. TNF-α concentration increased between 20 h and 36 h. This data indicates that MMP-2 plays an important role during the early acute developmental phase of oligofructose-induced equine laminitis.

Shiga Toxin Type 1 Activates Tumor Necrosis Factor-α Gene Transcription and Nuclear Translocation of the Transcriptional Activators Nuclear Factor-κB and Activator Protein-1

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 558-566 ◽  
Author(s):  
Ramesh Sakiri ◽  
Belakere Ramegowda ◽  
Vernon L. Tesh
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Translocation ◽  
Vascular Lesions ◽  
Transcriptional Activators ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Shiga toxins (Stxs) produced by Shigella dysenteriae 1 andEscherichia coli have been implicated in the pathogenesis of bloody diarrhea, acute renal failure, and neurologic abnormalities. The pathologic hallmark of Stx-mediated tissue damage is the development of vascular lesions in which endothelial cells are swollen and detached from underlying basement membranes. However, in vitro studies using human vascular endothelial cells demonstrated minimal Stx-induced cytopathic effects, unless the target cells were also incubated with the proinflammatory cytokines tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). These cytokines have been shown to upregulate the expression of the Stx-binding membrane glycolipid globotriaosylceramide (Gb3). We show here that purified Stx1 induces TNF secretion by a human monocytic cell line, THP-1, in a dose- and time-dependent manner. Treatment of cells with both lipopolysaccharides (LPS) and Stx1 results in augmented TNF production. Treatment with the nontoxic Gb3-binding subunit of Stx1 or with an anti-Gb3 monoclonal antibody did not trigger TNF production. Northern blot analyses show that Stx1 causes increased TNF-α production through transcriptional activation. Increased levels of TNF-α mRNA are preceded by the nuclear translocation of the transcriptional activators NF-κB and AP-1 and the loss of cytoplasmic IκB-α. These data are the first to show that, in addition to direct cytotoxicity, Stxs possess cellular signaling capabilities sufficient to induce the synthesis of cytokines that may be necessary for target cell sensitization and the development of vascular lesions.

Activated Protein C Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production by Inhibiting Activation of both Nuclear Factor-κB and Activator Protein-1 in Human Monocytes

2002 ◽  
Vol 88 (08) ◽  
pp. 267-273 ◽  
Author(s):  
Mehtap Yuksel ◽  
Mitsuhiro Uchiba ◽  
Seikoh Horiuchi ◽  
Hiroaki Okabe ◽  
Kenji Okajima
Keyword(s):  
Protein C ◽  
Tumor Necrosis ◽  
Activated Protein C ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Tnf Α ◽  
Target Sites ◽  
Factor Α ◽  
Necrosis Factor

SummaryActivated protein C (APC), an important natural anticoagulant, inhibits tumor necrosis factor-α (TNF-α) production and attenuates various deleterious events induced by lipopolysaccharide (LPS), contributing thereby to a significant reduction of mortality in patients with severe sepsis. In this study, we investigated the mechanism(s) by which APC inhibits TNF-α production by LPS-stimulated human monocytes in vitro. Although APC inhibited LPS-induced TNF-α production in a concentration-dependent fashion, diisopropyl fluorophosphate-treated APC, an active-site-blocked APC, had no effect. APC inhibited both the binding of nuclear factor-κB (NF-κB) to target sites and the degradation of IκBα. APC also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that APC inhibited LPS-induced TNF-α production by inhibiting the activation of both NF-κB and AP-1 and that the inhibitory activity of APC might depend on its serine protease activity. These results would at least partly explain the mechanism(s) by which APC reduces the tissue injury seen in animal models of sepsis and in patients with sepsis.

scholarly journals PKCϵ is involved in JNK activation that mediates LPS-induced TNF-α, which induces apoptosis in macrophages

2003 ◽  
Vol 285 (5) ◽  
pp. C1235-C1245 ◽  
Author(s):  
Mònica Comalada ◽  
Jordi Xaus ◽  
Annabel F. Valledor ◽  
Carlos López-López ◽  
Daniel J. Pennington ◽  
...  
Keyword(s):  
Cell Model ◽  
Primary Cultures ◽  
Signaling Mechanism ◽  
Major Function ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Jnk Activation ◽  
Necrosis Factor

Lipopolysaccharide (LPS) is a powerful stimulator of macrophages and induces apoptosis in these cells. Using primary cultures of bone marrow-derived macrophages, we found that the autocrine production of tumor necrosis factor-α (TNF-α) has a major function in LPS-induced apoptosis. LPS activates PKC and regulates the different mitogen-activated protein kinases (MAPK). We aimed to determine its involvement either in the secretion of TNF-α or in the induction of apoptosis. Using specific inhibitors and mice with the gene for PKCϵ disrupted, we found that LPS-induced TNF-α-dependent apoptosis is mostly mediated by PKCϵ, which is not directly involved in the signaling mechanism of apoptosis but rather in the process of TNF-α secretion. In our cell model, all three MAPKs were involved in the regulation of TNF-α secretion, but at different levels. JNK mainly regulates TNF-α transcription and apoptosis, whereas ERK and p38 contribute to the regulation of TNF-α production, probably through posttranscriptional mechanisms. Only JNK activity is mediated by PKCϵ in response to LPS and so plays a major role in TNF-α secretion and LPS-induced apoptosis. We demonstrated in macrophages that LPS involving PKCϵ regulates JNK activity and produces TNF-α, which induces apoptosis.

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