IFN regulatory factor (IRF)-2(-/-) mice are significantly more resistant to LPS challenge than wild-type littermates, and this was correlated with increased numbers of apoptotic Kupffer cells. To assess the generality of this observation, and to understand the role of IRF-2 in apoptosis, responses of peritoneal macrophages from IRF-2(+/+) and IRF-2(-/-) mice to apoptotic stimuli, including the ...

We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes. Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11. Sustained stimulation (>2 h) of LPS-primed caspase-1-de...

The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, ...

Caspase-1 is a key player during the initiation of pro-inflammatory innate immune responses, activating pro-IL-1β in so-called inflammasomes. A subset of patients with recurrent febrile episodes and systemic inflammation of unknown origin harbor mutations in CASP1 encoding caspase-1. CASP1 variants result in reduced enzymatic activity of caspase-1 and impaired IL-1β secretion. The apparent para...

Proinflammatory cytokines, such as interleukin-1 beta (IL-1β), are important mediators of psoriasis. Ubiquitin conjugating enzyme E2 L3 (UBE2L3), an enzyme, is thought to be indirect target IL-1β secretion by binding ubiquitin ligases (E3s) tripartite motif-containing protein 21 (TRIM21). However, its role in the psoriasis remains unknown. In this study, we found that UBE2L3 expression was decr...

Introduction Caspase-1 is a proinflammatory enzyme that is activated by the NLRP3 inflammasome in response to endoplasmic reticulum (ER) stress independent of the classical unfolded protein response. This finding linked ER stress to chronic inflammatory diseases. In patients suffering from unexplained recurrent febrile episodes we detected several genetic variants of CASP1 leading to reduced en...

alzheimer's disease (ad), the most ordinary form of dementia and extracellular accumulation of amyloid-β (aβ) in senile plaques, is an important and a main event in the pathogenesis of ad. deposition of aβ peptide initiates a spectrum of cellular responses that are interposed by the resident neuroimmune cells of the brain, the microglia. recently, a novel inflammasome signaling  pathway ha...

Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nuc...