Figure 3.

NFκB-dependent signaling as a central hub in inflammation. Various models of inflammatory-driven pathologies generated in larvae or adult zebrafish have identified NFκB signaling as part of the disease onset, progression, or recovery process. (A). In an adult model of epileptic seizure induced by pentylenetetrazole, the HMGB1/TLR4/NFκB pathway generates deleterious inflammation that results in a convulsive behavior [310]. (B). In larvae, atp1b1a mutation results in psoriasis-like phenotype and skin malignancy, through activation of the PI3K-AKT-mTORC1-NFκB-MMP9 pathway, which promotes keratinocytes overgrowth and invasiveness of epidermal layers [314]. (C). In contrast to these deleterious effects, NFκB pro-inflammatory signaling is required for cardiac regeneration as exemplified in an adult model of genetic cardiomyocyte ablation where NFκB-dependent upregulation of gata4-controled genes permits cardiomyocyte proliferation and epicardial infiltration [315]. (D). Infection of zebrafish larvae by Influenza A virus (IAV) induces a neutrophil-dependent activation of NFκB in skeletal muscles, upregulating pro-inflammatory cytokines such as IL1β and CXCL8 and generating sustained muscle damage that mimics Duchenne muscular dystrophy [316].