Hydrogen peroxide in neutrophil inflammation: Lesson from the zebrafish
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).
References (116)
- et al.
Resolvins and protectins in the termination program of acute inflammation
Trends Immunol.
(2007) - et al.
CCR7 is involved in the migration of neutrophils to lymph nodes
Blood
(2011) - et al.
ATP-mediated activation of the NADPH oxidase DUOX1 mediates airway epithelial responses to bacterial stimuli
J. Biol. Chem.
(2009) - et al.
Modeling cancer with flies and fish
Dev. Cell
(2019) - et al.
Using zebrafish to study pathways that regulate hematopoietic stem cell self-renewal and migration
Stem Cell Rep.
(2017) - et al.
Stress, inflammation, and defense of homeostasis
Mol. Cell
(2014) - et al.
Dynamics of neutrophil migration in lymph nodes during infection
Immunity
(2008) - et al.
Two hundred years of dermatology
J. Am. Acad. Dermatol.
(1998) - et al.
H2O2 in the induction of NF-kappaB-Dependent selective gene expression
Methods Enzymol.
(2013) - et al.
Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family
J. Biol. Chem.
(2000)
Activation of hypoxia-inducible factor-1alpha (Hif-1alpha) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model
Blood
Neutrophils and redox stress in the pathogenesis of autoimmune disease
Free Radic. Biol. Med.
Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB
Free Radic. Biol. Med.
Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer
Cell
Regulation of skin inflammation and angiogenesis by EC-SOD via HIF-1alpha and NF-kappaB pathways
Free Radic. Biol. Med.
Interstitial leukocyte migration in vivo
Curr. Opin. Cell Biol.
Neutrophil extracellular traps (NETs) in autoimmune diseases: a comprehensive review
Autoimmun. Rev.
Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated activation of NFkappaB-inducing kinase
J. Biol. Chem.
Fish immunology
Curr. Biol.
Hydrogen peroxide sensing, signaling and regulation of transcription factors
Redox Biol.
Models of human psoriasis: zebrafish the newly appointed player
Dev. Comp. Immunol.
Immunology and zebrafish: spawning new models of human disease
Dev. Comp. Immunol.
The role of neutrophils in autoimmune diseases
Immunol. Lett.
In vivo real-time visualization of leukocytes and intracellular hydrogen peroxide levels during a zebrafish acute inflammation assay
Methods Enzymol.
Zebrafish: an emerging model of vascular development and remodelling
Curr. Opin. Pharmacol.
Oxidative stress, transcription factors and chromatin remodelling in lung inflammation
Biochem. Pharmacol.
Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release
Curr. Biol.
A transgenic zebrafish model of neutrophilic inflammation
Blood
Calcium signalling in wound-responsive normal human urothelial cell monolayers
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.
The zebrafish: a fantastic model for hematopoietic development and disease
Wiley Interdiscip. Rev. Dev. Biol.
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2022, ChemosphereCitation Excerpt :IL-17 is a proinflammatory cytokine that plays an important role in inflammatory response (Kumari et al., 2009; Wang et al., 2014), and it could synergize with other cytokines, such as TNF-α, to amplify inflammatory response (Nirula et al., 2016). TNF-α is an important inflammatory cytokine that could activate NF-kΒ signaling pathway that involved in inflammation in fish (Correa et al., 2004; Martínez-Navarro et al., 2020). The mRNA levels of il-17c, tnf-α and nf-kb were significantly increased in metamifop-exposed groups in the present study.
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2022, Developmental and Comparative ImmunologyCitation Excerpt :Larval zebrafish possess a functionally comparable repertoire of blood cell lineages to mammals, including granulocytes and mononuclear cells (Tobin et al., 2012). Zebrafish innate immunity is detectable and active by 1–2 days post fertilization (dpf) while their adaptive immune system is morphologically and functionally mature after 4–6 weeks of development (Lam et al., 2004; Martínez-Navarro et al., 2020). This chronological separation facilitates the study of innate immunity in isolation at larval stages.
Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans
2021, Cell ReportsCitation Excerpt :Tissue damage induces transcription-independent signals involving Ca2+ and H2O2, which promote wound repair and inflammatory cell migration (Cordeiro and Jacinto, 2013). To stimulate immune cell chemotaxis, H2O2 promotes the modification of a thiol switch in the tyrosine kinase LYN (Yoo et al., 2011), the transcription of chemokines (de Oliveira et al., 2014, 2015; Martínez-Navarro et al., 2020), and wound repair and regenerative events in numerous organisms (Cordeiro and Jacinto, 2013; Suzuki and Mittler, 2012). Reactive oxygen species (ROS) have also recently been implicated in playing important roles in regulating actin and myosin accumulation at the wound site (Hunter et al., 2018; Ponte et al., 2020; Xu and Chisholm, 2014a).
Monobutyl phthalate can induce autophagy and metabolic disorders by activating the ire1a-xbp1 pathway in zebrafish liver
2021, Journal of Hazardous MaterialsCitation Excerpt :Zebrafish is an excellent experimental model fish with well-developed organs and phylogeny. Its liver structure and function are very similar to mammals, and it has been widely used in toxicology research (Martínez-Navarro et al., 2020; Ma et al., 2020). Our recent study found that MBP can induce disorders of the zebrafish liver antioxidant system (Jiao et al., 2020).
- 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.