Abstract
The clinical manifestation of hyperuricaemia, known as hyperuricaemia nephropathy, is relatively common. Its pathophysiology is largely based on chronic inflammation in circulatory and renal tissues. Toll-like receptor 4 (TLR4), a subclass of innate immune receptors, detects both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), initiating inflammatory and immune responses that lead to the release of pro-inflammatory cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). These cytokines are pivotal in renal inflammation, especially in conditions like hyperuricaemia, acute renal injury, ischemia-reperfusion injury, and acute renal failure. The nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune signaling complex, plays a central role in inflammation. It finely regulates the activation of caspase-1 and the production and secretion of the pro-inflammatory cytokine IL-1β, mediating and amplifying the inflammatory cascade response. Activation of TLR4 indirectly promotes the assembly of the NLRP3 inflammasome by regulating the nuclear factor kappa B (NF-κB) signaling pathway, thereby amplifying the inflammatory process and playing a significant pro-inflammatory role in hyperuricaemia nephropathy. TLR4 and NLRP3 inflammasome are anticipated to be novel markers and therapeutic targets for assessing treatment efficacy and prognosis in hyperuricaemia nephropathy. This paper provides a comprehensive overview of the structural composition and biological functions of TLR4 and NLRP3 inflammasome and systematically reviews their relevance in the pathogenesis of hyperuricaemia nephropathy.