Could synergistic interactions among reactive oxygen species, proteinases, membrane-perforating enzymes, hydrolases, microbial hemolysins and cytokines be the main cause of tissue damage in infectious and inflammatory conditions?

Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc.

Download Full-text

Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation

International Journal of Inflammation ◽

10.1155/2012/678190 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Nhat-Tu Le ◽

James P. Corsetti ◽

Janet L. Dehoff-Sparks ◽

Charles E. Sparks ◽

Keigi Fujiwara ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Subsequent Development ◽

Hdl Cholesterol ◽

Specific Protein ◽

Oxygen Species ◽

Cardiac Events ◽

Inflammatory Conditions ◽

Endothelial Inflammation ◽

Coronary Events

Although the exact mechanism through which NADPH oxidases (Nox’s) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relationship between ROS and endothelial inflammation will be provided in this review. Particularly, a crucial role for specific protein SUMOylation in endothelial inflammation will be presented. Given that SUMOylation of specific proteins leads to increased endothelial inflammation, targeting specific SUMOylated proteins may be an elegant, effective strategy to control inflammation. In addition, the involvement of ROS production in increasing the risk of recurrent coronary events in a sub-group of non-diabetic, post-infarction patients with elevated levels of HDL-cholesterol will be presented with the emphasis that elevated HDL-cholesterol under certain inflammatory conditions can lead to increased incidence of cardiovascular events.

Download Full-text

Reactive oxygen species mediated tissue damage in high energy proton irradiated mouse brain

Molecular and Cellular Biochemistry ◽

10.1007/s11010-011-1056-2 ◽

2011 ◽

Vol 360 (1-2) ◽

pp. 189-195 ◽

Cited By ~ 12

Author(s):

Sudhakar Baluchamy ◽

Prabakaran Ravichandran ◽

Vani Ramesh ◽

Zhenhua He ◽

Ye Zhang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Mouse Brain ◽

Tissue Damage ◽

Reactive Oxygen ◽

High Energy ◽

Oxygen Species ◽

High Energy Proton ◽

Energy Proton

Download Full-text

Heterocycle Thiazole Compounds Exhibit Antifungal Activity through Increase in the Production of Reactive Oxygen Species in the Cryptococcus neoformans-Cryptococcus gattii Species Complex

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02700-16 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 11

Author(s):

Nívea Pereira de Sá ◽

Caroline Miranda de Lima ◽

Cleudiomar Inácio Lino ◽

Paulo Jorge Sanches Barbeira ◽

Ludmila de Matos Baltazar ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cryptococcus Neoformans ◽

Antioxidant System ◽

Reactive Oxygen ◽

Systemic Infection ◽

Oxygen Species ◽

Content Type ◽

Synergistic Interactions ◽

Novel Drugs ◽

Show Evidence

ABSTRACT Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, subacute, or chronic systemic infection involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazole compounds 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system. The tested compounds exhibited MICs ranging from 0.25 to 2 μg/ml against Cryptococcus neoformans strains H99 and KN99α. Interestingly, the knockout strains for Cu oxidase and sarcosine oxidase were resistant to thiazoles. MIC values of thiazole compounds 1, 2, and 4 against these mutants were higher than for the parental strain. After the treatment of C. neoformans ATCC 24067 (or C. deneoformans) and C. gattii strain L27/01 (or C. deuterogattii) with thiazoles, we verified an increase in intracellular reactive oxygen species (ROS). Also, we verified the synergistic interactions among thiazoles and menadione, which generates superoxides, with fractional inhibitory concentrations (FICs) equal to 0.1874, 0.3024, 0.25, and 0.25 for the thiazole compounds 1, 2, 3, and 4, respectively. In addition, thiazoles exhibited antagonistic interactions with parasulphonatephenyl porphyrinato ferrate III (FeTPPS). Thus, in this work, we showed that the action of these thiazoles is related to an interference with the antioxidant system. These findings suggest that oxidative stress may be primarily related to the accumulation of superoxide radicals.

Download Full-text

IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in the generation of reactive oxygen species

10.1101/2020.03.04.975094 ◽

2020 ◽

Author(s):

Sandrine Huot ◽

Cynthia Laflamme ◽

Paul R. Fortin ◽

Eric Boilard ◽

Marc Pouliot

Keyword(s):

Reactive Oxygen Species ◽

Immune Cells ◽

Immune Complexes ◽

Tissue Damage ◽

Reactive Oxygen ◽

Surface Expression ◽

Human Neutrophils ◽

Ros Production ◽

Oxygen Species ◽

Key Players

AbstractAutoimmune complexes are an important feature of several autoimmune diseases such as lupus, as they contribute to tissue damage through the activation of immune cells. Neutrophils, key players in lupus, interact with immune complexes through Fc gamma receptors (FcgR). Incubation of neutrophils with aggregated-IgGs caused degranulation and increased the surface expression of FcgRI within minutes in a concentration-dependent fashion. After 30 min, IgG aggregates (1 mg/ml) up-regulated FcgRI by 4.95 ± 0.45-fold. FcgRI-positive neutrophils reached 67.24% ± 6.88% on HA-IgGs stimulated neutrophils, from 3.12% ± 1.62% in non-stimulated cells, ranking IgG-aggregates among the most potent known agonists. FcgRIIa, and possibly FcgRIIIa, appeared to mediate this up-regulation. Also, FcgRI-dependent signaling proved necessary for reactive oxygen species (ROS) production in response to IgG-aggregates. Finally, combinations of bacterial materials with aggregates dramatically boosted ROS production. This work suggests FcgRI as an essential component in the response of human neutrophils to immune complexes leading to the production of ROS, which may help explain how neutrophils contribute to tissue damage associated with immune complex-associated diseases, such as lupus.

Download Full-text