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The inflammasome is a multiprotein complex that mediates the activation of caspase-1, which promotes secretion of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18, as well as 'pyroptosis', a form of cell death induced by bacterial pathogens. Members of the Nod-like receptor family, including NLRP1, NLRP3 and NLRC4, and the adaptor ASC(More)
The Nlrp3 inflammasome is critical for the activation of caspase-1 in response to danger signals and particulate matter. However, its role in sterile inflammation remains unclear because prestimulation of phagocytic cells with microbial molecules is required for caspase-1 activation. We show here that exposure of macrophages and dendritic cells to TNF-alpha(More)
Tumor-derived exosomes have been shown to induce various immunomodulatory effects. However, the underlying signaling pathways are poorly understood. Here, we analyzed the effects of ex vivo-derived exosomes on monocytic cell differentiation/activation using THP-1 cells as model. We isolated exosomes from various body fluids such as amniotic fluid, liver(More)
The significance of bacterial RNA recognition for initiating innate immune responses against invading pathogens has only recently started to be elucidated. Bacterial RNA is an important trigger of inflammasome activation, resulting in caspase-1-dependent cleavage of pro-IL-1β into the active form. It was reported previously that prolonged treatment with(More)
Naturally occurring nucleotide modifications within RNA have been proposed to be structural determinants for innate immune recognition. We tested this hypothesis in the context of native nonself-RNAs. Isolated, fully modified native bacterial transfer RNAs (tRNAs) induced significant secretion of IFN-α from human peripheral blood mononuclear cells in a(More)
The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to(More)
We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an antibody against the gp80 unit of the(More)
Endogenous danger signals released from necrotic cells are thought to be sensed by phagocytes leading to secretion of IL-1alpha and neutrophilic recruitment. However, the mechanisms for IL-1alpha production and IL-1alpha-mediated sterile inflammation remain poorly understood. We report here that necrotic cell extracts elicited little secretion of CXCL1 and(More)