Hydrogen peroxide inhibits IL-12 p40 induction in macrophages by inhibiting c-rel translocation to the nucleus through activation of calmodulin protein

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1513-1520 ◽  
Author(s):  
Nooruddin Khan ◽  
Sheikh Showkat Rahim ◽  
Chandra Sekhar Boddupalli ◽  
Sheikh Ghousunnissa ◽  
Samavedan Padma ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Immune Response ◽  
Antimicrobial Activity ◽  
The Body ◽  
Interleukin 12 ◽  
Oxygen Species ◽  
H2o2 Treatment ◽  
Ifn Γ

Although the antimicrobial activity of reactive oxygen species (ROSs) is well defined, the role of ROSs in regulating the immune response of the body is not well understood. We now provide evidence that hydrogen peroxide (H2O2), a major component of ROSs, inhibits interleukin-12 (IL-12) p40 and IL-12 p70 induction in murine macrophages and catalase pretreatment prevents H2O2-mediated down-regulation of IL-12. Endogenous accumulation of H2O2/ROSs in macrophages treated with alloxan resulted in IL-12 p40 inhibition. Although nuclear expression of both p50 and p65 NF-κB increased on H2O2 exposure, nuclear c-rel level was inhibited. Overexpression of c-rel restored IL-12 p40 on stimulation with lipopolysaccharide plus IFN-γ during H2O2 treatment. H2O2 did not inhibit c-rel induction in cytosol; however, it prevented the transport of c-rel from cytosol to the nucleus. H2O2 activated calmodulin (CaM) protein in the cytosol, which subsequently sequestered c-rel in the cytosol preventing its transport to the nucleus. The CaM inhibitor trifIuoperazine increased both nuclear c-rel and IL-12 p40 levels in H2O2-treated macrophages, emphasizing a role of CaM in these processes. H2O2/ROSs thus down-regulate IL-12 induction in macrophages by a novel pathway inhibiting c-rel translocation to the nucleus through activation of CaM protein.

scholarly journals Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

2002 ◽  
Vol 9 (2) ◽  
pp. 348-351 ◽  
Author(s):  
Donato Torre ◽  
Filippo Speranza ◽  
Massimo Giola ◽  
Alberto Matteelli ◽  
Roberto Tambini ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Interleukin 12 ◽  
Th2 Cytokines ◽  
Th1 And Th2 Cytokines ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Th1 Cytokines ◽  
Th1 And Th2

ABSTRACT The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-γ, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ± 2.8 pg/ml; controls, 3.2 ± 0.7 pg/ml) and IFN-γ (39.2 ± 67.6 pg/ml; controls, 8.4 ± 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ± 2.6 pg/ml), whereas IFN-γ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ± 200.4 pg/ml and 56.6 ± 38.4 pg/ml, respectively; controls, 17.4 ± 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ± 1.2 pg/ml; controls, 2.4 ± 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ± 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-γ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.

Role of reactive oxygen species-generating enzymes and hydrogen peroxide during cadmium, mercury and osmotic stresses in barley root tip

Planta ◽  
2009 ◽  
Vol 231 (2) ◽  
pp. 221-231 ◽  
Author(s):  
Ladislav Tamás ◽  
Igor Mistrík ◽  
Jana Huttová ◽  
L’ubica Halušková ◽  
Katarína Valentovičová ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Reactive Oxygen ◽  
Barley Root ◽  
Root Tip ◽  
Oxygen Species ◽  
Barley Root Tip

scholarly journals Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Gammella ◽  
Stefania Recalcati ◽  
Gaetano Cairo
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Cell Signaling ◽  
Hydroxyl Radical ◽  
Iron Homeostasis ◽  
Storage Proteins ◽  
Oxygen Species ◽  
Physiologic Role

Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.

scholarly journals Interleukin-1 Receptor-Associated Kinase 4 Is Essential for Initial Host Control of Brucella abortus Infection

2011 ◽  
Vol 79 (11) ◽  
pp. 4688-4695 ◽  
Author(s):  
Fernanda S. Oliveira ◽  
Natália B. Carvalho ◽  
Ana Paula M. S. Brandão ◽  
Marco Túlio R. Gomes ◽  
Leonardo A. de Almeida ◽  
...  
Keyword(s):  
Immune Response ◽  
Brucella Abortus ◽  
Interleukin 1 ◽  
Bacterial Pathogen ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Ifn Γ

ABSTRACTBrucella abortusis a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Recent studies have revealed that Toll-like receptor (TLR)-initiated immune response toBrucellaspp. depends on myeloid differentiation factor 88 (MyD88) signaling. Therefore, we decided to study the role of the interleukin-1 receptor-associated kinase 4 (IRAK-4) in host innate immune response againstB. abortus. AfterBrucellainfection, it was shown that the number of CFU in IRAK-4−/−mice was high compared to that in IRAK-4+/−animals only at 1 week postinfection. At 3 and 6 weeks postinfection, IRAK-4−/−mice were able to control the infection similarly to heterozygous animals. Furthermore, the type 1 cytokine profile was evaluated. IRAK-4−/−mice showed lower production of systemic interleukin-12 (IL-12) and gamma interferon (IFN-γ). Additionally, a reduced percentage of CD4+and CD8+T cells expressing IFN-γ was observed compared to IRAK-4+/−. Further, the production of IL-12 and tumor necrosis factor alpha (TNF-α) by macrophages and dendritic cells from IRAK-4−/−mice was abolished at 24 h after stimulation withB. abortus. To investigate the role of IRAK-4 in mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, macrophages were stimulated withB. abortus, and the signaling components were analyzed by protein phosphorylation. Extracellular signal-regulated kinase 1 (ERK1) and ERK2 and p38 as well as p65 NF-κB phosphorylation was profoundly impaired in IRAK-4−/−and MyD88−/−macrophages activated byBrucella. In summary, the results shown in this study demonstrated that IRAK-4 is critical to trigger the initial immune response againstB. abortusbut not at later phases of infection.

scholarly journals Reactive oxygen species and oocyte aging: Role of superoxide, hydrogen peroxide, and hypochlorous acid

2008 ◽  
Vol 44 (7) ◽  
pp. 1295-1304 ◽  
Author(s):  
Anuradha P. Goud ◽  
Pravin T. Goud ◽  
Michael P. Diamond ◽  
Bernard Gonik ◽  
Husam M. Abu-Soud
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Hypochlorous Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Oocyte Aging

scholarly journals The Role of Oxidative Stress and Antioxidant Balance in Pregnancy

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Elsayed Metwally ◽  
Dildar Hussain Kalhoro ◽  
Muhammad Saleem Kalhoro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Gestational Diabetes ◽  
Embryo Implantation ◽  
Fetal Loss ◽  
The Body ◽  
Oxygen Species ◽  
In Pregnancy

It has been widely known that oxidative stress disrupts the balance between reactive oxygen species (ROS) and the antioxidant system in the body. During pregnancy, the physiological generation of ROS is involved in a variety of developmental processes ranging from oocyte maturation to luteolysis and embryo implantation. While abnormal overproduction of ROS disrupts these processes resulting in reproductive failure. In addition, excessive oxidative stress impairs maternal and placental functions and eventually results in fetal loss, IUGR, and gestational diabetes mellitus. Although some oxidative stress is inevitable during pregnancy, a balancing act between oxidant and antioxidant production is necessary at different stages of the pregnancy. The review aims to highlight the importance of maintaining oxidative and antioxidant balance throughout pregnancy. Furthermore, we highlight the role of oxidative stress in pregnancy-related diseases.

scholarly journals NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation

2018 ◽  
Vol 115 (30) ◽  
pp. 7765-7770 ◽  
Author(s):  
Wei Li ◽  
Jessica F. Young ◽  
Jianjun Sun
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Follicle Cells ◽  
Matrix Metalloproteinase 2 ◽  
Oxygen Species ◽  
Follicle Rupture

Ovarian reactive oxygen species (ROS) are believed to regulate ovulation in mammals, but the details of ROS production in follicles and the role of ROS in ovulation in other species remain underexplored. In Drosophila ovulation, matrix metalloproteinase 2 (MMP2) is required for follicle rupture by degradation of posterior follicle cells surrounding a mature oocyte. We recently demonstrated that MMP2 activation and follicle rupture are regulated by the neuronal hormone octopamine (OA) and the octopamine receptor in mushroom body (OAMB). In the current study, we investigated the role of the superoxide-generating enzyme NADPH oxidase (NOX) in Drosophila ovulation. We report that Nox is highly enriched in mature follicle cells and that Nox knockdown in these cells leads to a reduction in superoxide and to defective ovulation. Similar to MMP2 activation, NOX enzymatic activity is also controlled by the OA/OAMB-Ca2+ signaling pathway. In addition, we report that extracellular superoxide dismutase 3 (SOD3) is required to convert superoxide to hydrogen peroxide, which acts as the key signaling molecule for follicle rupture, independent of MMP2 activation. Given that Nox homologs are expressed in mammalian follicles, the NOX-dependent hydrogen peroxide signaling pathway that we describe could play a conserved role in regulating ovulation in other species.

scholarly journals Reactive oxygen species are involved in the signaling of equine sperm chemotaxis

Reproduction ◽  
2020 ◽  
Vol 159 (4) ◽  
pp. 423-436 ◽  
Author(s):  
Ayelen Moreno-Irusta ◽  
Esteban M Dominguez ◽  
Clara I Marín-Briggiler ◽  
Arturo Matamoros-Volante ◽  
Ornella Lucchesi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Energy Metabolism ◽  
Concentration Gradient ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Sperm Chemotaxis ◽  
Pka Pathway

Sperm chemotaxis may facilitate the finding of the oocyte. Only capacitated spermatozoa can orient their movement by chemotaxis, which as well as capacitation, is regulated in part by the cAMP-PKA pathway. Reactive oxygen species (ROS) are produced during sperm capacitation which is closely related to chemotaxis. Then, the ROS participation in the chemotactic signaling can be expected. Here we studied the role of ROS in the chemotaxis signaling of equine spermatozoa which produce high quantities of ROS because of their energy metabolism. The level of capacitated and chemotactic spermatozoa was increased with 0.1 and 0.2 mM hydrogen peroxide (H2O2), which was involved in the chemotactic signaling. By combining a concentration gradient of H2O2 with inhibitors/chelators of some of the signaling pathway elements, we showed that the activation of NOX (membrane NADPH oxidase) increases the intracellular ROS which activate the chemotaxis AMPc-PKA pathway. Our results provide evidence about the participation of ROS in the chemotactic signaling mediated by progesterone (P).

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