Figure 2
Steps in the processing and release of IL-1 induced by IL-1. (1) Primary blood monocytes, tissue macrophages or dendritic cells are activated by either mature IL-1β or the IL-1α precursor with the formation of the IL-1 receptor complex heterodimer comprised of the IL-1RI with IL-1RAcP. (2) Approximation of the intracellular TIR domains. (3) Recruitment of MyD88 and phosphorylation of IL-1R–associated kinases (IRAKs) and inhibitor of NFκB kinase β (IKKβ). (4) Transcription of IL-1β. (5) Translation into the IL-1β mRNA takes place on polysomes. IL-1β mRNA is not bound to actin microfilaments but rather intermediate filaments. (6) ATP released from the activated monocyte/macrophage accumulates extracellularly.51 (7) Activation of the P2X7 receptor by ATP. (8) Efflux of potassium from the cell after ATP binding to P2X7 receptor. (9) Fall in intracellular levels of potassium. (10) The fall in intracellular potassium levels triggers the assembly of the components of the caspase-1 inflammasome with the conversion of procaspase-1 to active caspase-1. (11) Caspase-1 is found in the secretory lysosome together with the IL-1β precursor and lysosomal enzymes.53 Active caspase-1 cleaves the IL-1β precursor in the secretory lysosome, generating the active, carboxyl-terminal mature IL-1β. (12) An influx of calcium with an increase in intracellular calcium levels. The rise in intracellular calcium activates phosphatidylcholine-specific phospholipase C and calcium-dependent phospholipase A. (13) The release of mature IL-1β, the IL-1β precursor, and the contents of the secretory lysosomes by exocytosis in the absence of cell death. (14) Processing of the IL-1β precursor in the cytosol. Rab39a, a member of the GTPase family, contributes to the secretion of by helping traffic IL-1β from the cytosol into a vesicle compartment. Exocytosis is another mechanism described in mouse macrophages. (15) Mature IL-1β exists the cells via loss in membrane integrity, associated with the release of lactic dehydrogenase or microvesicles. TRAF indicates TNF receptor-associated factor.

Steps in the processing and release of IL-1 induced by IL-1. (1) Primary blood monocytes, tissue macrophages or dendritic cells are activated by either mature IL-1β or the IL-1α precursor with the formation of the IL-1 receptor complex heterodimer comprised of the IL-1RI with IL-1RAcP. (2) Approximation of the intracellular TIR domains. (3) Recruitment of MyD88 and phosphorylation of IL-1R–associated kinases (IRAKs) and inhibitor of NFκB kinase β (IKKβ). (4) Transcription of IL-1β. (5) Translation into the IL-1β mRNA takes place on polysomes. IL-1β mRNA is not bound to actin microfilaments but rather intermediate filaments. (6) ATP released from the activated monocyte/macrophage accumulates extracellularly.51  (7) Activation of the P2X7 receptor by ATP. (8) Efflux of potassium from the cell after ATP binding to P2X7 receptor. (9) Fall in intracellular levels of potassium. (10) The fall in intracellular potassium levels triggers the assembly of the components of the caspase-1 inflammasome with the conversion of procaspase-1 to active caspase-1. (11) Caspase-1 is found in the secretory lysosome together with the IL-1β precursor and lysosomal enzymes.53  Active caspase-1 cleaves the IL-1β precursor in the secretory lysosome, generating the active, carboxyl-terminal mature IL-1β. (12) An influx of calcium with an increase in intracellular calcium levels. The rise in intracellular calcium activates phosphatidylcholine-specific phospholipase C and calcium-dependent phospholipase A. (13) The release of mature IL-1β, the IL-1β precursor, and the contents of the secretory lysosomes by exocytosis in the absence of cell death. (14) Processing of the IL-1β precursor in the cytosol. Rab39a, a member of the GTPase family, contributes to the secretion of by helping traffic IL-1β from the cytosol into a vesicle compartment. Exocytosis is another mechanism described in mouse macrophages. (15) Mature IL-1β exists the cells via loss in membrane integrity, associated with the release of lactic dehydrogenase or microvesicles. TRAF indicates TNF receptor-associated factor.

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