Inflammasomes: too big to miss
Andrea Stutz, … , Douglas T. Golenbock, Eicke Latz
Andrea Stutz, … , Douglas T. Golenbock, Eicke Latz
Published December 1, 2009
Citation Information: J Clin Invest. 2009;119(12):3502-3511. https://doi.org/10.1172/JCI40599.
View: Text | PDF
Science in Medicine

Inflammasomes: too big to miss

Abstract

Inflammation is the coordinated immune response to harmful stimuli that appear during infections or after tissue damage. Cells of the innate immune system are the central players in mediating inflammatory tissue responses. These cells are equipped with an array of signaling receptors that detect foreign molecular substances or altered endogenous molecules that appear under situations of stress. This review provides an overview of recent progress in elucidating the molecular mechanisms that lead to inflammatory reactions. We discuss the current knowledge of the mechanisms leading to the activation of cytoplasmic, multimolecular protein complexes, termed “inflammasomes,” which regulate the activity of caspase-1 and the maturation and release of IL-1β.

Authors

Andrea Stutz, Douglas T. Golenbock, Eicke Latz

×

Figure 2

Inflammasomes form large multimolecular complexes that control the activity of caspase-1.

Options: View larger image (or click on image) Download as PowerPoint
Inflammasomes form large multimolecular complexes that control the activ...
(i) Activation of cytokine receptors or pattern recognition receptors such as TLRs leads to the induction of pro–IL-1β and NLRP3. (ii) In a second step, NLRP3 inflammasome assembly is triggered by low intracellular potassium levels and the binding of a putative ligand that is generated by proteolytic activity after lysosomal damage or by the action of ROS. The assembled NLRP3 inflammasome results in activation of caspase-1, which proteolytically activates IL-1β family cytokines. The produced pro-inflammatory IL-1β family cytokines can act on other cell types or act in a feed-forward loop. High intracellular oxygen tension can also lead to direct deactivation of caspase-1.