Caspase-3 targets pro-interleukin-1β (IL-1β) to restrict inflammation.

The interleukin (IL)-1 family of cytokines plays a pivotal role in immune responses. Among the members of IL-1 family, IL-1β is synthesized as an inactive precursor (pro-IL-1β) and becomes active upon cleavage, which is typically facilitated by inflammasomes through caspase-1. In our research, we explored the potential role of caspase-3 in the cleavage of pro-IL-1β and found that caspase-3 cleaves pro-IL-1β, specifically at Asp26. Moreover, we found that in the absence of caspase-3 cleavage, the release of active IL-1β via the inflammasome is increased. Our study introduces pro-IL-1β as a new substrate for caspase-3 and suggests that caspase-3-mediated cleavage has the potential to suppress IL-1β-mediated inflammatory responses.