UW Cancer Center Johnson Creek

Introduction: Our lab has previously demonstrated that mice treated with recombinant Interleukin-13 (IL13) post myocardial infarction (MI) demonstrate improved cardiac function through IL13 directly signaling to macrophages. While treatment with IL13 improves heart function, it has no effect on cardiac fibrosis post MI. Macrophages respond to IL13 through a receptor comprised of IL-4Rα and IL13Ra1. Paradoxically, when IL-4Rα is knocked out from macrophages, treatment with IL13 post MI no longer improves cardiac function but instead increases scar area of the heart by almost 50% compared to vehicle control. This suggests that IL13 is also signaling to myofibroblasts to promote fibrosis and that macrophages are suppressing this activity. Hypothesis: We hypothesize that IL13 directly signals to cardiac myofibroblasts to aggravate scarring, as these cells express the IL13 receptor and largely contribute to fibrotic scarring in the post MI setting. Methods: To test this hypothesis, we are utilizing a Cre-lox system to knock out IL-4Rα from myofibroblasts and macrophages in mice and then subject mice to MI and IL13 administration. Scar size and heart function are assessed over a 28-day period following MI. We’ve compared this double knockout genotype to mice that only have IL-4Rα knocked out of myofibroblasts, mice that only have IL-4Rα knocked out of macrophages, and wildtype control mice. Results: Our data shows that when IL-4Rα is knocked out of both myofibroblasts and macrophages, treatment with IL13 results in less fibrosis compared to the macrophage IL-4Rα knockout group. Conclusion: Our data suggests that, knocking out the IL-4Rα receptor from both myofibroblasts and macrophages indeed rescues the scar phenotype. Findings from this study will lead to novel mechanisms by which macrophages interact with cardiac cell types to influence post MI healing.

Reacting to changes on a page is a big part of modern web application development. Although this has always been possible to some degree with anchor links and form submit buttons, the introduction of an events system made it possible to write code that adjusts to user input without the need to reload or changing the current page. You can probably see how this complements the ability to send Ajax requests as well. Since Internet Explorer version 4 (with the introduction of Microsoft’s Trident layout engine) and Netscape Navigator version 2 (along with the first JavaScript implementation), it has been possible to listen for DOM events in order to provide a more dynamic user experience in the browser. The first implementation of this model was quite limited. But as the browser evolved via standardization, so did the events system. Today, we have a fairly elegant native API for listening to and triggering both standardized DOM events and custom events. You’ll see throughout this chapter how you can make use of events in modern browsers to accomplish various tasks.