Nitric Oxide Production and Signaling in Inflammation

The Immunopharmacology Research Group, University of Tampere Medical School and Research Unit, Tampere University Hospital, Tampere, Finland.
Current Drug Targets - Inflammation & Allergy 09/2005; 4(4):471-9. DOI: 10.2174/1568010054526359
Source: PubMed


Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. It possesses cytotoxic properties that are aimed against pathogenic microbes, but it can also have damaging effects on host tissues. NO reacts with soluble guanylate cyclase to form cyclic guanosine monophosphate (cGMP), which mediates many of the effects of NO. NO can also interact with molecular oxygen and superoxide anion to produce reactive nitrogen species that can modify various cellular functions. These indirect effects of NO have a significant role in inflammation, where NO is produced in high amounts by inducible nitric oxide synthase (iNOS) and reactive oxygen species are synthesized by activated inflammatory cells. The present review deals with NO production and signaling in inflammation, especially in relation to human neutrophils and eosinophils.

Download full-text


Available from: Hannu Kankaanranta, Feb 12, 2015
38 Reads
  • Source
    • "tic effect or anti - apoptotic effect of NO has been described in various cells . Apoptosis in human B lymphocytes is suppressed by low - dose NO generated by nitric oxide synthase ( NOS ) ( Mannick et al . , 1994 ) , whereas excessive NO reacts with superoxide anion radicals to form peroxynitrite , leading to the activation of apoptosis cascade ( Korhonen et al . , 2005 ) . Previous studies have shown that M . hyopneumoniae , M . hyorhinis , and M . synoviae stimulate excessive production of NO in the RAW 264 . 7 cell line , human gastric carcinoma AZ - 521 cell Fig . 4 . Effects of LAMP treatment on PARP cleavage , Bax / Bcl - 2 ratio , and phosphorylation of p38 / ERK MAPK in PBMCs . Phosphorylation "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mycoplasma hyopneumoniae is the causative agent of swine enzootic pneumonia (EP), a disease that causes considerable economic losss in swine industry. Lipid-associated membrane proteins (LAMPs) of mycoplasma play important roles in causing mycoplasma diseases. The present study explores the pathogenic mechanisms of M. hyopneumoniae LAMPs by elucidating their role in modulating the inflammation, apoptosis, and relevant signaling pathways of peripheral blood mononuclear cells (PBMCs) of pig. LAMP treatment inhibited the growth of PBMCs. Up-regulation of cytokines, such as IL-6 and IL-1β, as well as increased production of nitric oxide (NO) and superoxide anion were all detected in the supernatant of LAMPs-treated PBMCs. Furthermore, flow cytometric analysis using dual staining with annexin-V-FITC and propidium iodide (PI) showed that LAMPs of M. hyopneumoniae induced a time-dependent apoptosis in lymphocyts and monocytes from PBMCs, which was blocked by NOS inhibitor or antioxidant. In addition, LAMPs induced the phosphorylation of p38, the ratio of pro-apoptotic Bax protein to anti-apoptotic Bcl-2, activation of caspase-3 and caspase-8, and poly ADP-ribose polymerase (PARP) cleavage in PBMCs. These findings demonstrated that M. hyopneumoniae LAMPs induced the production of proinflammatory cytokines, NO and reactive oxygen species (ROS), and apoptosis of PBMCs in vitro through p38 MAPK and Bax/Bcl-2 signaling pathways, as well as caspase activation.
    Veterinary Microbiology 11/2014; 175(1). DOI:10.1016/j.vetmic.2014.11.013 · 2.51 Impact Factor
  • Source
    • "The reaction between NO and superoxide anion is very rapid and forms peroxynitrite, which can lead to formation of nitrotyrosine (a marker for indirectly detecting peroxynitrite). The rate constant for this reaction is about three times greater than the rate of superoxide decomposition catalyzed by superoxide dismutase (Korhonen et al. 2005). Lipid peroxidation and protein carbonylation were significantly elevated after the overuse model, and a significant reduction was observed after treatment with phonophoresis plus AuNPs (Fig. 5a, 5b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study described here was to investigate the effects of pulsed ultrasound and gold nanoparticles (AuNPs) on behavioral, inflammatory and oxidative stress parameters in an experimental model of overuse. Wistar rats performed 21 d of exercise on a treadmill at different intensities and were exposed to ultrasound in the presence or absence of AuNPs. The overuse model promoted behavioral changes and increased creatine kinase, superoxide dismutase and glutathione peroxidase activity, as well as the levels of superoxide, nitrotyrosine, nitric oxide, thiobarbituric acid reactive substance, carbonyl, tumor necrosis factor α and interleukin-6. These values were significantly decreased by AuNPs and by AuNPs plus ultrasound. Catalase activity remained unchanged and the glutathione level increased significantly after exposure to AuNPs plus ultrasound. These results suggest a susceptibility to anxiety as well as elevated levels of oxidative stress. However, therapeutic interventions with AuNPs plus ultrasound reduced the production of oxidants and oxidative damage and improved the anti-oxidant defense system.
    Ultrasound in Medicine & Biology 11/2014; 41(1). DOI:10.1016/j.ultrasmedbio.2014.08.020 · 2.21 Impact Factor
  • Source
    • "A pronounced increase in NO levels has been described in ALS [26], and oxidative stress is a common downstream mechanism by which nigral dopamine neurons are damaged in PD [27]. ROS is additionally generated by the activation of several inflammatory enzymes, for example the expression of inducible nitric oxide synthase (iNOS) is under the transcriptional control of a variety of inflammatory cytokines, and the expression of proinflammatory mediators appears to be redox sensitive [28],[29]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1mT; frequency, 50-Hz) on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2-, which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT activity and a rise in O2- levels. Together these studies support the further evaluation of ELF-EMF exposure in cellular and in vivo preclinical models to define mechanisms potentially impacted in humans.
    PLoS ONE 08/2014; 9(8):e104973. DOI:10.1371/journal.pone.0104973 · 3.23 Impact Factor
Show more