The Pyroptotic Cell Death Effector Gasdermin D Is Activated by Gout-Associated Uric Acid Crystals but Is Dispensable for Cell Death and IL-1β Release.

The pyroptotic cell death effector gasdermin D (GSDMD) is required for murine models of hereditary inflammasome-driven, IL-1β-dependent, autoinflammatory disease, making it an attractive therapeutic target. However, the importance of GSDMD for more common conditions mediated by pathological IL-1β activation, such as gout, remain unclear. In this study, we address whether GSDMD and the recently described GSDMD inhibitor necrosulfonamide (NSA) contribute to monosodium urate (MSU) crystal-induced cell death, IL-1β release, and autoinflammation.

Expanding Neutrophil Horizons: New Concepts in Inflammation.

Research into neutrophil biology in the last 10 years has uncovered a number of unexpected aspects of this still mysterious innate immune cell. Advances in technology have allowed visualisation of neutrophil trafficking to sites of inflammation, and, remarkably, neutrophils have been observed to depart from the scene in what has been termed reverse migration. There has also been increasing appreciation of the heterogeneity of neutrophils with ongoing categorisation of neutrophil subsets, including myeloid-derived suppressor cells and low-density granulocytes.

Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular Traps via a Distinct Molecular Pathway.

Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals.

XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.

X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear.

Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR).

Anti-citrullinated peptide antibody: death of the rheumatoid factor?

Early diagnosis and treatment of rheumatoid arthritis (RA) is necessary to prevent joint damage and long-term disability. High rates of false-negative and false-positive results of the rheumatoid factor (RF) test make it generally unhelpful in the early diagnosis of RA. A new clinical test for RA--the anti-citrullinated peptide antibody (ACPA) test--is now widely available in Australia.

Complementary and alternative medicines in ankylosing spondylitis: a cross-sectional study.

Prevalence of dietary complementary and alternative medicine (CAM) and consultation with a CAM practitioner was examined in a cross-sectional study of 75 AS patients. Seventy one of 75 (94.7%) study participants reported previous or current CAM use.