Inflammasomes are neuroprotective targets for sex steroids.
Neuroinflammation in the central nervous system is triggered by toxic stimuli or degenerative events, orchestrates the interplay of brain-intrinsic immune cells and neighboring neural cells, and sequentially allows leukocyte extravasation from the periphery into the brain parenchyma. During the inflammatory cascade, immune-competent cells become activated and secrete a plethora of cytokines and chemokines which form a local inflammatory signaling network important for warding off harmful stimuli to the host but are likewise necessary to preserve damaged brain tissue. Inflammatory responses are initiated by extra- and intra-cellular pathogen and danger-associated receptors. These signals are processed by multi-protein complexes termed inflammasomes which trigger the production of biologically active interleukins-1 and 18 after the cleavage of caspase-1. Estrogens and progesterone are neuroprotective and anti-inflammatory in diverse disease models of the brain in particular under acute inflammatory conditions such as stroke and traumatic brain injury. Both steroids are able to attenuate pro-inflammatory cytokine activity. Recent literature and our own studies provide convincing evidence that the anti-inflammatory potency of these steroids result from a complex interaction with the inflammasome activation and their up-stream regulatory network of miRNAs in brain-intrinsic innate immune cells. This article examines steroid-inflammasome interactions in the brain during brain injury and illuminates the importance of regulation initial upstream events during neuroinflammation. This article is part of a Special Issue entitled 'Steroid Perspectives'.
Institute of Neuroanatomy, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany.
Alexander
A
Slowik
Institute of Neuroanatomy, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany. Electronic address: cbeyer@ukaachen.de.
Cordian
C
Beyer
D000818:Animals; D001921:Brain / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology; D004967:Estrogens / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D020078:Neurogenic Inflammation / Q000276:immunology*; D011374:Progesterone / Q000276:immunology*
D004967:Estrogens; D058847:Inflammasomes; D011374:Progesterone
Astroglia; Estrogen; Inflammasome; Microglia; Neuroinflammation; Progesterone