IL-1β promotes tubulointerstitial injury in 
MPO-ANCA-associated glomerulonephritis

Abstract

Sterile inflammation leads to the formation of ANCA-mediated neutrophil extracellular traps (NETs), which may stimulate macrophages and dendritic cells via TLR4 and induce NF-κB-dependent mRNA expression and translation of pro-IL-1β. Simultaneously, damage-associated molecular pattern signals resulting from NETs promote NLRP3 inflammasome-dependent processing and release mature active IL-1β. Sterile inflammation utilizing the NLRP3 inflammasome might be a characteristic reaction limited to the tubulointerstitium. Thus, neutralizing IL-1β may be a promising strategy to suspend the progress of TII and improve the prognosis of chronic kidney disease resulting from ANCAGN. .

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia

“…Afterwards, NF-κB stimulates macrophage infiltration of renal interstitium and the apoptosis of renal tubular cells by increasing the production of proinflammatory chemokines [ 18 ]. In order to investigate if NLRP3 inflammasome takes part in the development of tubulointerstitial inflammation and injury Tashiro et al assessed kidney biopsy specimens of 28 patients with TI [ 19 ]. Researchers discovered that IL-β1 was elevated in all samples and positively correlated with the severity of the tubulointerstitial injury.…”

“…Researchers discovered that IL-β1 was elevated in all samples and positively correlated with the severity of the tubulointerstitial injury. Moreover, there was a positive correlation of NLRP3 mRNA with the severity of TI as well, which indicates that NLRP3 inflammasome is associated with TI and might contribute to its development [ 19 ]. As was described above, NLRP3 inflammasome activates not only IL-β1 and IL-18 but also gasdermin D, and Li et al reported that gasdermin D can lead to kidney injury through the induction of renal tubular cell pyroptosis in the course of treatment with cisplatin [ 20 ].…”

Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease

“…In the Tokushima rat model, activation of NLRP3 inflammasomes accelerates macrophage recruitment and M1 polarization, promoting CXCL12 and high mobility group box-1 release in the proximal tubule, and contributing to the progression of diabetic nephropathy [ 49 ]. It is also observed clinically that NLRP3 inflammasomes are activated and mature IL-1β is released in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis patients [ 50 ].…”

The Role of Neutrophil Extracellular Traps in Post‐Injury Inflammation

“…TLR4 seems to be responsible for this kind of neutrophil activity in particular as many publications demonstrated their interaction via HMGB-1 [55], superoxide production [69], platelet activation [29] or IL-1β [70]. Oxidised low-density lipoprotein, which has been implicated as an independent risk factor in various acute or chronic inflammatory diseases including SIRS, was also found to act as a NETosis trigger via TLRs [71]. More recently, TLR9 has come into focus in NET research as mtDNA and other DAMPs that are recognised by TLR9 showed high potential to induce NETs in trauma patients [39], in liver ischemia/reperfusion injury [3] or due to surgical stress [72].…”