Abstract
Neutrophils are important effector cells during inflammation, which play complex roles. Therefore, investigating the regulation of neutrophil accumulation during inflammation might provide targets for treating related diseases. In the present study, we generated a ripk3-deficient zebrafish line to study the roles of Ripk3 in neutrophil-related inflammation. The homeostatic hematopoiesis and cytokine expression of the ripk3-deficient larvae were unaltered. The ripk3-deficient larvae with caudal fin fold injury exhibited similar neutrophil enrichment with wild-type larvae, suggesting that Ripk3 is not essential for non-infectious inflammatory responses. When challenged with lipopolysaccharide (LPS), the ripk3-deficient larvae showed significantly less neutrophil accumulation in the injection site and differential expression of several key cytokines. Ripk3 inhibitors could also attenuate neutrophil accumulation in wild-type larvae, indicating that Ripk3 could serve as a candidate target for inflammation treatment. In summary, our study indicated that Ripk3 has an essential role in LPS-induced inflammatory responses. It was suggested that the ripk3-deficient zebrafish might be applied in developing infectious disease models, while Ripk3 also has potential as an inflammation-treatment target.
Highlights
Inflammation is an immune response triggered by biological, physical, and chemical inflammatory factors in various tissues and organs of the body
By generating and further characterizing a zebrafish ripk3-deficient line, we found that the ripk3 deficiency perturbed neutrophil enrichment and affected cytokine expressions upon LPS challenge
We found that the LPS-injected larvae showed of Sudan black (SB) staining showed no significant difference in the population apparent local neutrophil accumulation at 2 hpi compared with of neutrophils between ripk3-deficient larvae and WT larvae at the control group (Fig. S2A, B)
Summary
Inflammation is an immune response triggered by biological, physical, and chemical inflammatory factors in various tissues and organs of the body. RIPK3 plays an essential role in lipopolysaccharide (LPS)-induced acute inflammatory responses, which are not dependent on caspases [16]. The potential role of Ripk in regulating neutrophil-associated inflammation has never been reported in zebrafish. Cytokines, and neutrophil accumulation during non-infectious we applied the caudal fin fold injury to ripk3-deficient inflammation. By using zebrafish as a model, we deficient and WT larvae exhibited almost no neutrophil at the demonstrate that Ripk plays key roles in infectious inflammation caudal fin fold region before treatment, while similar neutrophil and could serve as a therapeutic target for inflammatory-related accumulation was found at 5 hpi with no significant difference disease treatment. In non-infectious inflammatory responses, the ripk deficiency does not affect the recruitment of neutrophils
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