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 (ROS) have been implicated to play important roles in this process. However, the cellular and molecular basis underlying the actions of IL-1β and ROS 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 ROS 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 ROS signaling and critical for the directional migration, but not the basal random movement, of neutrophils. In contrast, the NADPH oxidase-mediated ROS 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 ROS 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.
State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China;
Bo
B
Yan
Institute of Molecular Medicine, Peking University, Beijing 100871, China;
Peidong
P
Han
State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China;
Lifeng
L
Pan
State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China;
Wei
W
Lu
Institute of Molecular Medicine, Peking University, Beijing 100871, China;
Jingwei
J
Xiong
State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China;
Mingjie
M
Zhang
Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Cell Biology, Southern Medical University, Guangzhou 510515, China; and.
Wenqing
W
Zhang
Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, State Key Laboratory Breeding Base of Eco-Environments and Bio-Resources of the Three Gorges Area, School of Life Science, Southwest University, Chongqing 400715, China.
Li
L
Li
State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China; zilong@ust.hk swu_lili@126.com.
Zilong
Z
Wen
D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015027:Zebrafish / Q000276:immunology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000276:immunology*
D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D017382:Reactive Oxygen Species; D029961:Zebrafish Proteins; D019255:NADPH Oxidases