Potent pro-inflammatory cytokine ( , ). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production . Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells . Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 . Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (, ). Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection .
Subcellular locations: Cytoplasm, Cytosol, Secreted, Lysosome, Secreted, Extracellular exosome
The precursor is cytosolic . In response to inflammasome-activating signals, such as ATP for NLRP3 inflammasome or bacterial flagellin for NLRC4 inflammasome, cleaved and secreted ( ). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore . In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation . The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 .
Expressed in activated monocytes/macrophages (at protein level).