Differential levels of reactive oxygen species in murine preadipocyte 3T3-L1 cells cultured on type I collagen molecule-coated and gel-covered dishes exert opposite effects on NF-κB-mediated proliferation and migration

2018 ◽  
Vol 52 (9) ◽  
pp. 913-928 ◽  
Author(s):  
Xiaoling Liu ◽  
Xinyu Long ◽  
Weiwei Liu ◽  
Guodong Yao ◽  
Yeli Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type I Collagen ◽  
Reactive Oxygen ◽  
Collagen Molecule ◽  
Type I ◽  
Oxygen Species ◽  
And Migration ◽  
Cells Cultured ◽  
Proliferation And Migration

Stimulatory Auto-Antibodies to the PDGF Receptor in Patients with Chronic GVHD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 454-454
Author(s):  
Attilio Olivieri ◽  
Silvia Svegliati ◽  
Nadia Campelli ◽  
Michele Maria Luchetti ◽  
Silvia Trappolini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Type I Collagen ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Type I ◽  
Collagen Gene ◽  
Pdgf Receptor ◽  
Oxygen Species ◽  
Normal Human

Abstract Background Experimental data are consistent with the hypothesis that activation of the PDGF receptor (PDGFR) is characteristic of scleroderma (SSc) fibroblasts and may contribute to their activation. We have recently demonstrated that fibroblasts from SSc patients contain high Ha Ras and ROS (Reactive Oxygen Species) levels and constitutive activation of ERK1/2 (Svegliati et al: JBC in press). Furthermore, SSc patients have circulating auto-antibodies against the PDGFR which induce type I collagen gene expression in normal human fibroblasts through the Ha Ras-ERK1/2- ROS pathway (Svegliati et al: Submitted). These findings suggest that anti PDGFR auto-antibodies play a pivotal role in the pathogenesis of scleroderma. Clinical chronic graft-versus-host disease (cGVHD) can show manifestations that are very similar to those of SSc. Although it is conceivable that the two diseases can share a similar pathophysiological mechanism there are no data supporting this assumption. In view of these considerations we tested the hypothesis that patients with cGVHD have serum auto-antibodies that stimulate PDGFR and activate collagen gene expression in fibroblasts. Methods Serum from 7 patients with extensive cGVHD showing scleroderma-like features either in the skin or in the lung was analyzed for the presence of stimulatory autoantibodies to PDGFR. Patients receiving allogeneic transplantation, but without any signs of cGVHD were used as controls. The median F-U after transplant was 23 months (range 16–36) in patients with cGVH and 42 (range 9–51) in the control group. The assay was carried by incubating purified IgG of the patients with mouse embryo fibroblasts carrying inactive copies of PDGFR α or β chains (PDGFR −/−) or the same cells expressing PDGFR α or β, respectively. Production of reactive oxygen species was assayed in the presence or absence of specific PDGFR inhibitors. The antibodies were characterized by immunoprecipitation, immunoblotting and absorption experiments in primary human fibroblasts and endothelial cells. Result Stimulatory antibodies to the PDGFR were selectively found in all patients with cGVHD and fibrotic lesions. The antibodies specifically recognized PDGFR, induced tyrosine phosphorylation and ROS accumulation. Their activity was completely and selectively abolished by pre-incubation with cells expressing PDGFR α or β chains or by PDGF receptor tyrosine kinase inhibitor. Anti-PDGFR antibodies induced selectively Ha-Ras-ERK1/2 and ROS cascade and stimulated the expression of type I collagen gene and myofibroblast phenotype conversion in normal human primary fibroblasts. Antibodies were absent in all controls. Conclusions Stimulatory auto-antibodies against PDGFR represent a specific hallmark of patients with cGVHD. Their biological activity on fibroblasts strongly argues for a causal role in the pathogenesis of the disease.

scholarly journals Reactive oxygen species oxidize STING and suppress interferon production

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lili Tao ◽  
Andrew Lemoff ◽  
Guoxun Wang ◽  
Christina Zarek ◽  
Alexandria Lowe ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Reactive Oxygen ◽  
Interferon Response ◽  
Cellular Respiration ◽  
Type I ◽  
Oxygen Species ◽  
Interferon Production ◽  
Dna Sensing ◽  
Cytoplasmic Dna

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

scholarly journals Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

2009 ◽  
Vol 11 (4) ◽  
pp. 747-764 ◽  
Author(s):  
Srikanth Pendyala ◽  
Irina A Gorshkova ◽  
Peter V. Usatyuk ◽  
Donghong He ◽  
Arjun Pennathur ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Human Lung ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Lung Endothelial Cells ◽  
And Migration

scholarly journals Reactive Oxygen Species as Essential Mediators of Cell Adhesion and Migration

2010 ◽  
Vol 98 (3) ◽  
pp. 576a ◽  
Author(s):  
Giuseppe Maulucci ◽  
Giovambattista Pani ◽  
Valentina Labate ◽  
Marina Mele ◽  
Emiliano Panieri ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Adhesion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Adhesion And Migration ◽  
And Migration

scholarly journals Inside-Out Signaling Pathways from Nuclear Reactive Oxygen Species Control Pulmonary Innate Immunity

2016 ◽  
Vol 8 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Sanjeev Choudhary ◽  
Istvan Boldogh ◽  
Allan R. Brasier
Keyword(s):  
Reactive Oxygen Species ◽  
Innate Immunity ◽  
Signaling Pathways ◽  
Nuclear Export ◽  
Reactive Oxygen ◽  
Small Gtpase ◽  
Early Gene ◽  
Type I ◽  
Oxygen Species ◽  
Ros Signaling

The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperates in the IIR. We discuss recent discoveries about 2 nuclear ROS signaling pathways controlling innate immunity. Nuclear ROS oxidize guanine bases to produce mutagenic 8-oxoguanine, a lesion excised by 8-oxoguanine DNA glycosylase1/AP-lyase (OGG1). OGG1 forms a complex with the excised base, inducing its nuclear export. The cytoplasmic OGG1:8-oxoG complex functions as a guanine nucleotide exchange factor, triggering small GTPase signaling and activating phosphorylation of the nuclear factor (NF)κB/RelA transcription factor to induce immediate early gene expression. In parallel, nuclear ROS are detected by ataxia telangiectasia mutated (ATM), a PI3 kinase activated by ROS, triggering its nuclear export. ATM forms a scaffold with ribosomal S6 kinases, inducing RelA phosphorylation and resulting in transcription-coupled synthesis of type I and type III interferons and CC and CXC chemokines. We propose that ATM and OGG1 are endogenous nuclear ROS sensors that transmit nuclear signals that coordinate with outside-in pattern recognition receptor signaling, regulating the IIR.

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