scholarly journals Respiratory Syncytial Virus Infection Induces a Reactive Oxygen Species-MSK1-Phospho-Ser-276 RelA Pathway Required for Cytokine Expression

2009 ◽  
Vol 83 (20) ◽  
pp. 10605-10615 ◽  
Author(s):  
Mohammad Jamaluddin ◽  
Bing Tian ◽  
Istvan Boldogh ◽  
Roberto P. Garofalo ◽  
Allan R. Brasier
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Response ◽  
Target Gene ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Target Gene Expression ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a human pathogen that induces airway inflammation, at least in part, by modulating gene expression programs in airway epithelial cells. The presence of RSV replication is detected by the intracellular retinoic acid-inducible gene I (RIG-I) RNA helicase that forms a productive signaling complex with the mitochondrion-anchored MAVS protein, resulting in nuclear translocation of the NF-κB transcription factor. Although nuclear translocation is a prerequisite for activation of the innate inflammatory response, recent studies show that separate pathways governing RelA activation are also required for target gene expression. In this study, we examine the mechanism of RelA phosphorylation and its requirement for RSV-induced gene expression. RSV infection produced a time-dependent RelA phosphorylation on serine (Ser) residues Ser-276 and Ser-536 in parallel with enhanced reactive oxygen species (ROS) stress. Inhibition of RSV-induced ROS inhibited formation of phospho-Ser-276 RelA without affecting phospho-Ser-536 RelA formation. RSV potently induced activation of cytoplasmic mitogen- and stress-related kinase 1 (MSK1) in an ROS-dependent manner. Inhibition of MSK1 using H89 and small interfering RNA knockdown both reduced RSV-induced phospho-Ser-276 RelA formation and expression of a subset of NF-κB-dependent genes. Direct examination of the role of phospho-Ser-276 in target gene expression by expression of a RelA Ser-276-to-Ala site mutation in RelA−/− mouse embryonic fibroblasts showed that the mutation was unable to mediate RSV-induced NF-κB-dependent gene expression. We conclude that RSV induces RelA activation in the innate inflammatory response via a pathway separate from that controlling RelA cytoplasmic release, mediated by ROS signaling to cytoplasmic MSK1 activation and RelA Ser-276 phosphorylation.

The protects of deep sea water against photoaging of HaCaT keratinocyte induced by UVB via suppression MMPs and MAPKs/NF-κB signaling pathway

2021 ◽  
Author(s):  
Xiaolei Ma ◽  
Duomo Duan ◽  
Baolong Xie ◽  
Xunliang Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Sea Water ◽  
Reactive Oxygen ◽  
Collagen Degradation ◽  
Ultraviolet B ◽  
Oxygen Species ◽  
Uvb Irradiation ◽  
The Impact

Abstract Ultraviolet radiation destroys skin through several harmful effects, like inducing reactive oxygen species, inflammatory response, and collagen degradation. In this study we researched the impact of deep seawater (DSW) on the photoaging of HaCaT keratinocytes induced by ultraviolet B (UVB). DSW can inhibit epidermal hyperplasia and collagen degradation, increase skin moisture and hydroxyproline content, thereby improving the macro and histopathological damage of skin under UVB irradiation. Besides, DSW can inhibit UVB-induced oxidative stress (OS), improve antioxidant enzyme activity and inhibit the cellular signal transduction pathway of inflammatory response. Results showed DSW curbed the UVB irradiated levels of reactive oxygen species, superoxide dismutase (SOD), oxidative enzyme, glutathione peroxidase (GSH-Px), proinflammatory cytokines (TNF-α, IL-6). DSW prevented UVB-induced photoaging by suppressing collagen disorientation and expression of MMPs induced by UVB. Moreover, Western blot analyses exhibited that DSW significantly lessened the protein levels of phosphorylated SAPK/JNK kinase, phosphorylated ERK1/2 kinase, and phosphorylated p38 kinase. Similarly, UVB induced nuclear translocation of nuclear factor kappa-B were diminished by treatment of DSW. Therefore, DSW may lessen skin OS and inflammatory response under UVB irradiation. These data suggest that DSW can be used as a potentially effective skin care and dietary supplement for attenuating UVB-induced premature skin aging.

Homocysteine induces VCAM-1 gene expression through NF-κB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants

2007 ◽  
Vol 293 (4) ◽  
pp. H2344-H2354 ◽  
Author(s):  
Maria Annunziata Carluccio ◽  
Maria Assunta Ancora ◽  
Marika Massaro ◽  
Marisa Carluccio ◽  
Egeria Scoditti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Mediterranean Diet ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Northern Analysis ◽  
Mrna Levels ◽  
Oxygen Species ◽  
Polyphenolic Antioxidants

Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-κB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-κB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 μmol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-κB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-κB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IκB-α and IκB-β by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47phox subunit. NF-κB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10−6 mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-κB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage.

scholarly journals Attenuation by Reactive Oxygen Species of Glucocorticoid Suppression on Proopiomelanocortin Gene Expression in Pituitary Corticotroph Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Koichi Asaba ◽  
Yasumasa Iwasaki ◽  
Masanori Yoshida ◽  
Masato Asai ◽  
Yutaka Oiso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Glucocorticoid Receptor ◽  
Negative Feedback ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

Abstract Up-regulation of hypothalamo-pituitary-adrenal axis is maintained during acute inflammation and/or infection, in the face of sustained elevation of plasma glucocorticoid hormone. Inflammatory stress is usually associated with high plasma cytokine levels and increased generation of reactive oxygen species (ROS) as well. In this study, we examined the effect of ROS on the negative feedback regulation of glucocorticoid in hypothalamo-pituitary-adrenal axis using AtT20 corticotroph cells in vitro. When the cells were treated with H2O2, glucocorticoid suppression on the proopiomelanocortin gene promoter activity was attenuated in a dose-dependent manner. H2O2 also inhibited the ligand-stimulated nuclear translocation of glucocorticoid receptor. The released glucocorticoid suppression by H2O2 was not observed when the cells were cotreated with antioxidants. Together, these results suggest that increased ROS generation in the oxidative redox state attenuates the glucocorticoid negative feedback system, at least in part, by interfering with the nuclear translocation of glucocorticoid receptor and eliminating the repression on proopiomelanocortin gene expression.

Co-regulation of Cxcl1 and versican in inflammatory response in UVB induced reactive oxygen species in the skin

2017 ◽  
Vol 86 (2) ◽  
pp. e80
Author(s):  
Chihiro Takemori ◽  
Makoto Kunisada ◽  
Flandiana Yogianti ◽  
Sugako Oka ◽  
Kunihiko Sakumi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Inflammatory Response ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function

2021 ◽  
Author(s):  
Jee Hyung Sohn ◽  
Yul Ji ◽  
Chang-Yun Cho ◽  
Hahn Nahmgoong ◽  
Sangsoo Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Brown Adipocytes ◽  
Erk Activation ◽  
Brown Adipose ◽  
Erk Inhibition ◽  
Glucose 6 Phosphate Dehydrogenase

Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PD<sup>mut</sup>) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to ERK activation. In BAT of G6PD<sup>mut</sup> mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PD<sup>mut</sup> mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis.

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