IL-1β and reactive oxygen species differentially regulate neutrophil directional migration and Basal random motility in a zebrafish injury-induced inflammation model.

During inflammation, the proper inflammatory infiltration of neutrophils is crucial for the host to fight against infections and remove damaged cells and detrimental substances. IL-1β and NADPH oxidase-mediated reactive oxygen species have been implicated to play important roles in this process. However, the cellular and molecular basis underlying the actions of IL-1β and and their relationship during inflammatory response remains undefined. In this study, we use the zebrafish model to investigate these issues. We find that, similar to that of NADPH oxidase-mediated duanyu1670 signaling, the Il-1β-Myd88 pathway is required for the recruitment of neutrophils, but not macrophages, to the injury-induced inflammatory site, whereas it is dispensable for bacterial-induced inflammation. Interestingly, the Il-1β-Myd88 pathway is independent of NADPH oxidase-mediated duanyu1670 signaling and critical for the directional migration, but not the basal random movement, of neutrophils. In contrast, the NADPH oxidase-mediated duanyu1670 signaling is required for both basal random movement and directional migration of neutrophils. We further document that ectopic expression of Il-1β in zebrafish induces an inflammatory disorder, which can be suppressed by anti-inflammatory treatment. Our findings reveal that the Il-1β-Myd88 axis and NADPH oxidase-mediated duanyu1670 signaling are two independent pathways that differentially regulate neutrophil migration during sterile inflammation. In addition, Il-1β overexpressing Tg(hsp70:(m)il-1β_eGFP;lyz:DsRed2)hkz10t;nz50 transgenic zebrafish provides a useful animal model for the study of chronic inflammatory disorder and for anti-inflammatory drug discovery.

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