IL-1B as a key cytokine to regulate infiltration of monocytes/macrophages in the brain in systemic inflammation

Abstract

Aims: Systemic inflammation can be a risk factor for developing cognitive dysfunctions and even Alzheimer’s disease. It is still unclear how systemic monocytes/macrophages respond after sterile inflammation. We aim to use zebrafish and tail amputation for investigating which factor can affect the influence of systemic inflammation in the brain. Methods: Zebrafish was used as an experimental model. Tg(coro1a:DsRed) transgenic fish was used to monitor microglia and macrophages. Tg(mpx:mCherry) was used for monitoring neutrophils, Tg(mepg1:GFP) was used for monitoring macrophages. We have used TALEN method to make knockout or mutation of IL-1β in zebrafish. Quantitative PCR and immunohistochemical staining were used for examination. Acridine orange and TUNEL were employed for labeling apoptotic cells. Tail amputation was performed at day 3 of embryos under anesthetization with tricaine. Results: Tail amputation recruited accumulation of monocytes/macrophages into the wound site in zebrafish tail. Surprisingly, an increased number of macrophages and microglia were also found in the brain, which was tissue-specific as no other organs showed a similar phenomenon. The expression of mRNA for different cytokines was also examined. Among which, IL-1β was significantly increased. Therefore, we prepared IL-1β knockout and mutated zebrafish. After amputation, the basal number of macrophages in the brain did not show any significant increase. We found an increased number of apoptotic cells in the brain after wound injury. IL-1β had a key role in regulating the migration of monocytes/macrophages. Conclusions: Our study demonstrated that IL-1β is a key player to regulate migration of monocytes/macrophages in the brain.