Galectin-9 regulates serum amyloid A-induced inflammasome activation in human neutrophils

Objective: The Nod-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome plays roles in host defense and the development of autoinflammation. Galection-9 (Gal-9), one of the β-galactoside binding lectins, plays important regulatory roles in autoimmune diseases. T cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3)/Gal-9 inhibitory interaction has been proposed in innate immune system. We investigate the role of Galectin-9 (Gal-9) on serum amyloid A (SAA)-induced inflammasome activation and IL-1β processing by human neutrophils. Results SAA stimulation induced the release of cleavage of IL-1β (p17) from neutrophils suggesting that SAA induces the inflammasome activation and subsequent processing of pro-IL-1β. ELISA data demonstrated that SAA stimulation also induced cleaved caspase-1 (p20) secretion from human neutrophils, and this release was suppressed by Gal-9 pretreatment. Gal-9 pretreatment diminished the SAA-induced cleaved IL-1β secretion, however, did not affect SAA-induced pro-IL-1β secretion from neutrophils. Furthermore, Gal-9 pretreatment suppressed SAA-induced intracellular accumulation of cleaved IL-1β, suggesting that Gal-9 functions as a negative regulator of SAA-induced inflammasome activation and may be a potential therapeutic target for the treatment of autoinflammatory disorders.