Inflammatory Response to Regulated Cell Death in Gout and Its Functional Implications

Abstract

Gout, a chronic inflammatory arthritis disease, is characterized by hyperuricemia and caused by interactions between genetic, epigenetic, and metabolic factors. Acute gout symptoms are triggered by the inflammatory response to monosodium urate crystals, which is mediated by the innate immune system and immune cells (e.g., macrophages and neutrophils), the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation, and pro-inflammatory cytokine (e.g., IL-1β) release. Recent studies have indicated that the multiple programmed cell death pathways involved in the inflammatory response include pyroptosis, NETosis, necroptosis, and apoptosis, which initiate inflammatory reactions. In this review, we explore the correlation and interactions among these factors and their roles in the pathogenesis of gout to provide future research directions and possibilities for identifying potential novel therapeutic targets and enhancing our understanding of gout pathogenesis.

Soluplus®-based dissolving microarray patches loaded with colchicine: towards a minimally invasive treatment and management of gout

“…These observations can be corroborated by previously reported mechanistic studies that highlight the inhibitory effect of CLC on inflammatory cytokines, such as TNF-α. 89 This anti-inflammatory effect is achieved mainly via the destabilisation of the microtubule network that inhibits the signal transduction of the TNF-α-NF-κB pathway, 91 which translates into the reduction of TNF-α post treatment with CLC.…”

“…Thus, it is postulated that, by inhibiting TNF-α release at an early stage in the TNF-α-NF-κB pathway, a reduction of inflammatory cell infiltration in subjects with gout during an acute inflammatory state could be achieved. 89,91 This suggests that CLC-loaded MAPs could potentially be an efficacious treatment for acute gout.…”

Aberrant messenger RNA expression in peripheral blood mononuclear cells is associated with gouty arthritis

“…Staphylococcus aureus tolerates an acidic environment and induces Ca 2+ overload when its invasion process is initiated on the surface of host cells, which eventually leads to necrotic cell death 58–60 . However, the effects of multiple forms of cell death, such as pyroptosis, apoptosis, necroptosis, and entotic cell death are involved in the pathogenesis of GA 61 . Therefore, these results may suggest that the “ Staphylococcus aureus infection” pathway may induce AGA by causing cell death.…”

Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials

“…And only Osteoporosis and Osteopenia included more than 1000 participants (1156), the rest of the diseases included less than 1000 participants. (5) This systematic review only included 8 types of inflammatory arthritis, and the others were not retrieved, which may be due to the fact that probiotics for inflammatory arthritis have just emerged and received less attention. (6) Many RCTs did not report adverse events, perhaps because they were not observed, or were not monitored.…”

“…(4) Drugs that lower uric acid levels (gout) (17). (5) Other related nutritional supplements. However, the above-mentioned drug-related adverse reactions are common and cannot guarantee remission, and are prone to drug resistance over time leading to treatment failure (18)(19)(20).…”