Caspase4driven

Caspase4driven is a term used in immunology and cell biology to describe cellular responses predominantly governed by activation of human caspase-4, an inflammatory caspase that operates in noncanonical inflammasome signaling. In response to intracellular components from Gram-negative bacteria, particularly lipopolysaccharide (LPS), caspase-4 can be activated and initiate pyroptotic cell death and related inflammatory signaling.

Mechanism: Activation involves binding of cytosolic LPS to the caspase-4 CARD, leading to autoproteolysis and cleavage of gasdermin D (GSDMD). The N-terminal fragment of GSDMD forms pores in the plasma membrane, causing cell lysis and release of inflammatory mediators. Caspase-4 activity can also trigger secondary activation of the canonical inflammasome, resulting in caspase-1–mediated processing of IL-1β and IL-18.

Biological significance: The caspase4driven pathway is prominently studied in human macrophages and dendritic cells, and it is implicated in host defense against Gram-negative bacteria as well as in sterile inflammatory responses. Dysregulation has been linked to septic shock and inflammatory diseases. Therapeutic strategies targeting caspase-4 signaling aim to modulate pyroptosis and cytokine release.

Terminology: The phrase caspase4driven is used to describe signaling cascades in which CASP4 activity is the primary driver of observed inflammatory outcomes, though it is often part of a broader network including other caspases and inflammasome components. It remains a descriptive, rather than formal, classification in current literature.