Hydrogen peroxide in neutrophil inflammation: Lesson from the zebrafish

doi:10.1016/j.dci.2019.103583

Developmental & Comparative Immunology

Volume 105, April 2020, 103583

https://doi.org/10.1016/j.dci.2019.103583 Get rights and content

Highlights

•
The zebrafish model has allowed visualization of Duox1-derived H₂O₂ tissue gradients.
•
H₂O₂ mediates neutrophil infiltration to inflamed tissue through Lyn-mediated direct recruitment.
•
H₂O₂ mediates neutrophil infiltration indirectly by the activation of several signaling pathways.
•
H₂O₂ to induce cxcl8 expression via histone covalent modifications.
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A H₂O₂/NF-κB/Duox1 positive feedback inflammatory loop operates in psoriasis.

Abstract

The zebrafish has become an excellent model for the study of inflammation and immunity. Its unique advantages for in vivo imaging and gene and drug screening have allowed the visualization of dual oxidase 1 (Duox1)-derived hydrogen peroxide (H₂O₂) tissue gradients and its crosstalk with neutrophil infiltration to inflamed tissue. Thus, it has been shown that H₂O₂ directly recruits neutrophils via the Src-family tyrosine kinase Lyn and indirectly by the activation of several signaling pathways involved in inflammation, such as nuclear factor κB (NF-κB), mitogen activated kinases and the transcription factor AP1. In addition, this model has also unmasked the unexpected ability of H₂O₂ to induce the expression of the gene encoding the key neutrophil chemoattractant CXC chemokine ligand 8 by facilitating the accessibility of transcription factors to its promoter through histone covalent modifications. Finally, zebrafish models of psoriasis have shown that a H₂O₂/NF-κB/Duox1 positive feedback inflammatory loop operates in this chronic inflammatory disorder and that pharmacological inhibition of Duox1, but not of downstream mediators, inhibits inflammation and restores epithelial homeostasis. Therefore, these results have pointed out DUOX1 and H₂O₂ as therapeutic targets for the treatment of skin inflammatory disorders, such as psoriasis.

Section snippets

The zebrafish model in biomedical research

Zebrafish (Danio rerio H.) is a small teleost fish (maximum size of 60 mm) that belongs to the family Cyprinidae and is originally from India and Pakistan regions (Mayden et al., 2007). For many decades, zebrafish has been a very popular aquarium fish and also an important research model in toxicology and developmental biology. Since its introduction in the science laboratory more than 50 years ago, its popularity in biomedical research has increased tremendously. Zebrafish has captured

Inflammation

In response to infections or tissue damage, stress or malfunction and upon activation of TLRs and other PRRs the innate immune system launches a pathophysiological response, termed as inflammation, with the main purpose of neutralizing the causative agent of the threat and starting the reparation of the injured tissues (Chovatiya and Medzhitov, 2014; Dempsey et al., 2003; Medzhitov, 2008; Ortega-Gomez et al., 2013; Schmid-Schonbein, 2006). The four cardinal signs of inflammation were already

Neutrophils: key players of inflammation

Neutrophils are the most abundant white-blood cells circulating in the human blood and are crucial pathogen-fighting immune cells (Gunzer, 2014; Mayadas et al., 2014; Mocsai, 2013; Nemeth and Mocsai, 2012). As for other blood cells, neutrophils are produced from hematopoietic progenitors in the bone marrow. Importantly and in case of emergency the granulocyte colony-stimulating factor (G-CSF) can induce neutrophil production up to 10 times in a process termed as “danger mobilization” or

Hydrogen peroxide: a pivotal regulator of neutrophil inflammation

Hydrogen peroxide (H₂O₂) was known and studied for several years as one of the main molecules produced by neutrophils as part of the leukocyte oxidative burst response involved in host defense (Dahlgren et al., 2019; Yoo and Huttenlocher, 2009) (Fig. 3). Recently this old molecule won a new role in inflammation since it has been shown to be produced after wounding (Niethammer et al., 2009; Razzell et al., 2013; Yoo et al., 2011) by the Dual oxidase 1 (DUOX1), a member of NOX protein family (

Chronic inflammatory diseases

The establishment of a chronic inflammation can be the starting point for a multitude of different chronic inflammation diseases, which are defined by long-term inflammatory processes directed at a particular endogenous or exogenous antigen (Heap and van Heel, 2009). The incidence of these diseases is being rapidly increased worldwide, mainly in the most developed countries, supposing a great impact for their national health systems. Taking only one example, of the ten leading causes of

Psoriasis, a chronic inflammatory skin disease

Psoriasis is a chronic, genetically influenced, remitting and relapsing scaly and inflammatory skin disorder, characterized by the appearance of red plaques covered with silvery scale that flakes away from the skin (Rendon and Schakel, 2019). Psoriatic plaques are often found on the elbows, scalp and knees but can also affect other parts of the body such as the face, feet and mucous membranes. It affects approximately 1–3% of the world's population (Greaves and Weinstein, 1995), and it is not

Conclusions and future directions

The zebrafish model has unique advantages for biomedical research and, in particular, to understand the relevance of oxidative stress in chronic inflammatory disorders and its crosstalk with neutrophilic inflammation. The possibility of in vivo tracking of immune cells together with the simultaneous visualization of H₂O₂ tissue gradients, the amenable genetic manipulation and high throughput drug screening make this model complimentary to other vertebrate species in the study of chronic

Acknowledgments

The work in our laboratory is funded by the Spanish Ministry of Science, Innovation and Universities (grant BIO2017-84702-R to VM and PhD fellowship to FJMN, both co-funded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds), Fundación Séneca, Agencia de Ciencia y Tecnología de la Región de Murcia (grant 20793/PI/18 to VM) and the University of Murcia (postdoctoral contracts to ABPO and DGM, and PhD fellowship to FJMM).

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¹: University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.

²: Department of Developmental & Molecular Biology and Department of Medicine (Hepatology), Marion Bessin Liver Research Center, Jack & Pearl Resnick Campus, 1300 Morris Park Ave., Bronx, 10461, NY, USA.

³: These authors contributed equally.

View full text

Hydrogen peroxide in neutrophil inflammation: Lesson from the zebrafish

Highlights

Abstract

Section snippets

The zebrafish model in biomedical research

Inflammation

Neutrophils: key players of inflammation

Hydrogen peroxide: a pivotal regulator of neutrophil inflammation

Chronic inflammatory diseases

Psoriasis, a chronic inflammatory skin disease

Conclusions and future directions

Acknowledgments

Trends Immunol.

Blood

J. Biol. Chem.

Dev. Cell

Stem Cell Rep.

Mol. Cell

Immunity

J. Am. Acad. Dermatol.

Methods Enzymol.

J. Biol. Chem.

Blood

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Cell

Free Radic. Biol. Med.

Curr. Opin. Cell Biol.

Autoimmun. Rev.

J. Biol. Chem.

Curr. Biol.

Redox Biol.

Dev. Comp. Immunol.

Dev. Comp. Immunol.

Immunol. Lett.

Methods Enzymol.

Curr. Opin. Pharmacol.

Biochem. Pharmacol.

Curr. Biol.

Blood

Cell Calcium

Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases

N. Engl. J. Med.

The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology

Physiol. Rev.

The role of nuclear factor-kappa B in cytokine gene regulation

Am. J. Respir. Cell Mol. Biol.

Purinergic regulation of epithelial transport

J. Physiol.

Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation

PLoS Biol.

Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis

Development

Centers for Disease Control and Prevention

The role of transcription-independent damage signals in the initiation of epithelial wound healing

Nat. Rev. Mol. Cell Biol.

Membrane wounding triggers ATP release and dysferlin-mediated intercellular calcium signaling

J. Cell Sci.

Intracellular neutrophil oxidants: from laboratory curiosity to clinical reality

J. Immunol.

A quantitative study of NF-kappaB activation by H2O2: relevance in inflammation and synergy with TNF-alpha

J. Immunol.

Duox1-derived H2O2 modulates Cxcl8 expression and neutrophil recruitment via JNK/c-JUN/AP-1 signaling and chromatin modifications

J. Immunol.

ATP modulates acute inflammation in vivo through Duox1-derived H2O2 production and NF-kB activation

J. Immunol.

Cxcl8 (IL-8) mediates neutrophil recruitment and behavior in the zebrafish inflammatory response

J. Immunol.

The art of war: innate and adaptive immune responses

Cell. Mol. Life Sci.

Localized bacterial infection induces systemic activation of neutrophils through Cxcr2 signaling in zebrafish

J. Leukoc. Biol.

The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish

Development

mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish

Blood

Mechanisms and function of DUOX in epithelia of the lung

Antioxidants Redox Signal.

Regulated hydrogen peroxide production by Duox in human airway epithelial cells

Am. J. Respir. Cell Mol. Biol.