Myeloid Cell-Derived Reactive Oxygen Species Externally Regulate the Proliferation of Myeloid Progenitors in Emergency Granulopoiesis

Kwak, Hyun-Jeong; Liu, Peng; Bajrami, Besnik; Xu, Yuanfu; Park, Shin-Young; Nombela‐Arrieta, César; Mondal, Subhanjan; Sun, Yan; Zhu, Haiyan; Chai, Li; Silberstein, Leslie E.; Cheng, Tao; Luo, Hongbo

doi:10.1016/j.immuni.2014.12.017

Cited by 96 publications

(111 citation statements)

References 58 publications

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“…Accordingly, we first examined whether IL-1β treatment and/or irradiation can induce ROS production in the BM. ROS levels in the BM were measured using Amplex Red, a colorless substrate that reacts with H 2 O 2 with 1:1 stoichiometry to produce highly fluorescent resorufin (Kwak et al, 2015; Zhu et al, 2017). Both irradiation (Figure 4B) and IL-1β (Figure 4C) significantly increased H 2 O 2 in the BM extracellular space.…”

Section: Resultsmentioning

confidence: 99%

Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation

et al. 2017

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SUMMARY Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1β positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1β from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1β glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation

et al. 2017

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“…C. difficile infection and subsequent trigger of inflammation results in significant increase in the levels of growth factors and molecules that influence emergency granulopoiesis (e.g. GM-CSF, G-CSF, IL-23, ROS) [60,61,63,64], thus it is likely that emergency granulopoiesis plays a key role in C. difficile disease pathogenesis. However, the exact contribution of emergency granulopoiesis and neutrophil turnover during C. difficile infection has not been studied by rigorous in vivo experimentation.…”

Section: Neutrophil-mediated Inflammation: Friend or Foe?mentioning

confidence: 99%

Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections

Jose

Madan

2016

Anaerobe

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Clostridium difficile is the most important cause of nosocomial infectious diarrhea in the western world. C. difficile infections are a major healthcare burden with approximately 500,000 new cases every year and an estimated annual cost of nearly $1 billion in the U.S. Furthermore, the infections are no longer restricted to health care facilities, and recent studies indicate spread of C. difficile infection to the community as well. The clinical spectrum of C. difficile infection ranges from asymptomatic colonization to severe diarrhea, fulminant colitis and death. This spectrum results from a complex interplay between bacterial virulence factors, the colonic microbiome and the host inflammatory response. The overall vigor of host inflammatory response is believed to be an important determinant of C. difficile disease severity, and a more robust immune response is associated with worse outcomes. Neutrophils are the primary cells that respond to C. difficile invasion and neutrophilic inflammation is the hallmark of C. difficile-associated disease. In this review, we will focus on the role of neutrophils (infiltration to infected tissue, pathogen clearance and resolution of inflammation) in the immuno-pathogenesis of C. difficile-associated disease (CDAD).

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“…Under infectious or inflammatory conditions, neutrophil granulopoiesis can be increased, typically termed “emergency granulopoiesis”, in order to restore homeostasis in the bone marrow after recruitment of neutrophils to peripheral sites (1). While IL-3, IL-6, G-CSF and GM-CSF have all been shown to contribute to emergency granulopoiesis, it has also been demonstrated that the production of reactive oxygen species (ROS) by bone marrow myeloid cells is critical for this process during infection (2). Neutrophils that traffic into tissues in the absence of infection or inflammation commonly become apoptotic rather than returning to circulation.…”

Section: Introductionmentioning

confidence: 99%

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes

Witter

Okunnu

Berg

2016

The Journal of Immunology

104

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Neutrophils have historically been characterized as first responder cells vital to host survival due to their ability to contain and eliminate bacterial and fungal pathogens. However, recent studies have shown that neutrophils participate in both protective and detrimental responses to a diverse array of inflammatory and infectious diseases. Although the contribution of neutrophils to extracellular infections has been investigated for decades, their specific role during intracellular bacterial infections has only recently been appreciated. During infection with the gram-positive intracellular pathogen Listeria monocytogenes, neutrophils are recruited from the bone marrow to sites of infection where they utilize novel bacterial sensing pathways leading to phagocytosis and production of bactericidal factors. This review summarizes the requirement of neutrophils during Listeria monocytogenes infection by examining both neutrophil trafficking and function during primary and secondary infection.

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Myeloid Cell-Derived Reactive Oxygen Species Externally Regulate the Proliferation of Myeloid Progenitors in Emergency Granulopoiesis

Cited by 96 publications

References 58 publications

Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation

Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation

Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes

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