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

The present study suggests pro-IL-1 β as a novel substrate of caspase-3. The activation of apoptotic signaling induces caspase-3 to cleave pro-IL-1β at the Asp26 site, and the generation of the Asp26 site restricts the inflammasome-mediated cleavage at the Asp117 site. Thus, caspase-3 prevents the release of mature IL-1β into the e xtracellular environment. The interleukin (IL)-1 family of cytokines plays a pivotal role in immune responses. Among the members of IL-1 family, IL-1 β 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, specifi cally at Asp26. Moreover, we found that in the absence of caspase-3 cleavage, the release of active IL-1βvia the inflammasome is increased. Our study introduces pro-IL-1 β as a new substrate for caspase-3 and suggests that caspase-3-mediated cleavage has the potential to suppress IL-1β-mediated inflammatory responses.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research