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Silica crystals are potent activators of the inflammasome that cause a fibrotic lung disease, called silicosis, with no effective treatment available. We report here that injection of silica crystals into the hindbrain ventricle of zebrafish embryos led to the initiation of local and systemic immune responses driven through both Toll-like receptors (TLR)- and inflammasome-dependent signaling pathways, followed by induction of pro-fibrotic markers. Genetic and pharmacological analysis revealed that the Nlrp3 inflammasome regulated silica crystal-induced inflammation and pyroptotic cell death, but not emergency myelopoiesis. In addition, Cxcl8a/Cxcr2-dependent recruitment of myeloid cells to silica crystals was required to promote emergency myelopoiesis and systemic inflammation. The zebrafish model of silicosis developed here shed light onto the molecular mechanisms involved in the activation of the immune system by silica crystals., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD + ) is the most important hydrogen carrier in cell redox reactions. It is involved in mitochondrial function and metabolism, circadian rhythm, the immune response and inflammation, DNA repair, cell division, protein-protein signaling, chromatin remodeling and epigenetics. Recently, NAD + has been recognized as the molecule of life, since, by increasing NAD + levels in old or sick animals, it is possible to improve their health and lengthen their lifespan. In this review, we summarize the contribution of NAD + metabolism to inflammation, with special emphasis in the major NAD + biosynthetic enzyme, nicotinamide phosphoribosyl transferase (NAMPT), and the NAD + -consuming enzyme, poly(ADP-ribose) polymerase (PARP). The extracurricular roles of these enzymes, i.e. the proinflammatory role of NAMPT after its release, and the ability of PARP to promote a novel form of cell death, known as parthanatos, upon hyperactivation are revised and discussed in the context of several chronic inflammatory diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 (H 2 O 2 ) tissue gradients and its crosstalk with neutrophil infiltration to inflamed tissue. Thus, it has been shown that H 2 O 2 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 H 2 O 2 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 H 2 O 2 /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 H 2 O 2 as therapeutic targets for the treatment of skin inflammatory disorders, such as psoriasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)