Role of ROS-Induced NLRP3 Inflammasome Activation in the Formation of Calcium Oxalate Nephrolithiasis

Abstract

Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.

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“…ROS exacerbate inflammation, which in turn increases ROS production [ 64 ]. Recent studies demonstrated that HMGB1 was stimulated by inflammatory bodies of NLRB, and HMGB1 could in turn facilitate the formation of inflammatory bodies of NLRP3, forming positive feedback of inflammation, thus sustaining or even intensifying the inflammatory cascade reaction and making acute inflammatory damage [ 65 , 66 ]. This was also manifested in our correlation analysis.…”

Cu-loaded polyurethane to reduce ureteral stent microbes adherence and regulation of the inflammation response to RAW264.7

“…The mechanism of regulating encrustation response to macrophage is shown in Figure 9. M 1 and its corresponding pro-inflammatory cytokines, TNF-α and IL-6, and oxidative stress molecules, property to promote the development of CaOx stones, were downregulated via diminishing the nuclear factor kB (NF-kB) signal pathway after contacting with PU-Cu stents (Song et al, 2016;Liu et al, 2022a). Lysosome rupture, ROS generation, and NLRP3 inflammasome activation were blocked in the process of macrophage engulfing (Jin et al, 2011).…”

“…In addition to lumen blocking, stones can also activate the inflammatory response of the human body and ultimately lead to tissue injury under the control of related inflammatory meditators (Li et al, 2020;Liu et al, 2022a). Macrophages play an important role in the early inflammatory response, and diverse cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) are secreted (Liu et al, 2022b).…”

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“…ROS also indirectly maintain the activity of this cascade by inactivating JNK‐inhibiting phosphatase 161 . Moreover, ROS can trigger NLRP3 activation to regulate macrophage pyroptosis 162 . In addition, ROS enhance the phosphorylation of IκB to activate NF‐κB 163 and participate in the activation of STAT1 and IRF5 164 .…”