Targeting toll-like receptor 4 and the NLRP3 inflammasome: Novel and emerging therapeutic targets for hyperuricaemia nephropathy

Authors

  • Chao Zhang Department of Nephrology, Yijishan Hospital of Wannan Medical College, Wuhu, China
  • Yanlang Yang Department of Nephrology, Yijishan Hospital of Wannan Medical College, Wuhu, China

DOI:

https://doi.org/10.17305/bb.2023.9838

Keywords:

Hyperuricaemia nephropathy, pathogenesis, inflammation, Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3)

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.

Targeting Toll-like receptor 4 (TLR4) and the NLRP3 inflammasome: Novel and emerging therapeutic targets for hyperuricaemia nephropathy

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Published

01-12-2023

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How to Cite

1.
Targeting toll-like receptor 4 and the NLRP3 inflammasome: Novel and emerging therapeutic targets for hyperuricaemia nephropathy. Biomol Biomed [Internet]. 2023 Dec. 1 [cited 2024 Feb. 25];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/9838