Inhibition of IL-18 reduces renal fibrosis after ischemia-reperfusion

Liu, Hua; Xu, Feng; Zhang, Tao; Huang, Jen-Fa; Guan, Qingbin; Wang, Hanbing; Huang, Qiong

doi:10.1016/j.biopha.2018.07.031

Cited by 42 publications

(30 citation statements)

References 34 publications

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“…It was already known that IL-1b alone was sufficient to induce EMT in different cells, including epithelial cells and cancer cells (33,34). IL-18 is also an important proinflammatory factor contributing to the development of organ fibrosis (35). Neutralization of IL-1b was reported to attenuate silica-induced lung fibrosis in mice (36).…”

Section: Discussionmentioning

confidence: 99%

Paricalcitol attenuates TGF‐β1–induced phenotype transition of human peritoneal mesothelial cells (HPMCs)viamodulation of oxidative stress and NLRP3 inflammasome

Kang

Kim

et al. 2018

FASEB j.

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Phenotype transition of mesothelial cells, such as epithelial‐to‐mesenchymal transition (EMT), is one of the early mechanisms of peritoneal fibrosis, which is mediated by oxidative stress and inflammation. Nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein oligomer that promotes the maturation of IL‐lβ and IL‐18. Paricalcitol is reported to exert an antiinflammatory effect; however, there are no studies as to whether paricalcitol modulates the activation of NLRP3 inflammasome. We investigated the role of NLRP3 inflammasome in peritoneal EMT with an exploration of the effect of paricalcitol on oxidative stress, NLRP3 inflammasome, and EMT of mesothelial cells. TGF‐βl‐induced EMT in human peritoneal mesothelial cells (HPMCs) was associated with an up‐regulation of NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), and ρrocasρase‐1, with an increased production of IL‐lβ and IL‐18, which was ameliorated by small interfering (si)NLRP3, siASC, caspase inhibitors, or neutralizing antibodies for IL‐lβ and IL‐18. TGF‐βl enhanced reactive oxygen species generation with an increase in NADPH oxidase (NOX) activity and mitochondrial NOX4 production. Paricalcitol alleviated TGF‐βl‐induced EMT and the NLRP3 inflammasome, which was associated with a down‐regulation of NOX activity by interfering with p47phox and p22phox interaction and mitochondrial NOX4 production in HPMCs. Taken together, paricalcitol ameliorated EMT of HPMCs via modulating an NOX‐dependent increase in the activity of NLRP3 inflammasome. Paricalcitol could be a novel approach to protect the peritoneum from the development of EMT and peritoneal fibrosis.—Ko, J., Kang, H.‐J., Kim, D.‐A., Ryu, E.‐S., Yu, M., Lee, H., Lee, H. K., Ryu, H.‐M., Park, S.‐H., Kim, Y.‐L., Kang, D.‐H. Paricalcitol attenuates TGF‐βl–induced phenotype transition of human peritoneal mesothelial cells (HPMCs) via modulation of oxidative stress and NLRP3 inflammasome. FASEB J. 33, 3035–3050 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Paricalcitol attenuates TGF‐β1–induced phenotype transition of human peritoneal mesothelial cells (HPMCs)viamodulation of oxidative stress and NLRP3 inflammasome

Kang

Kim

et al. 2018

FASEB j.

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“…IL-1β is a potential mediator of the crosstalk between inflammation and fibrosis and can generate a positive feedback cycle to dominate the secretory cytokine profile in cystic fibrosis (Otto, 2018;Chen et al, 2019). Additionally, the deletion or inhibition of IL-18 can alleviate cardiac or renal fibrosis in corresponding mouse models (Liang et al, 2018;Xiao et al, 2018). Several mechanisms underly how IL-1β, IL-18, and pyroptosis enhance inflammation and fibrosis after inflammasome activation.…”

Section: The Nlrp3 Inflammasome and Fibrosismentioning

confidence: 99%

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis

Ding

Wei

et al. 2020

Front. Pharmacol.

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Fibrosis is a common pathway followed by different organs after injury, and it can lead to parenchymal scarring, cellular dysfunction, and even organ failure. The NLRP3 inflammasome is a multiprotein complex composed of the sensor molecule NLRP3, the adaptor apoptosis-associated speck-like protein containing a CARD (ASC), and the effector protease caspase-1. Overactivation of the NLRP3 inflammasome triggers the abundant secretion of IL-1β and IL-18, induces pyroptosis, and promotes the release of a swathe of proinflammatory proteins, all of which contribute to fibrogenic processes in multiple organs. In recent years, screening bioactive natural compounds for NLRP3 inhibitors to alleviate fibrosis has gained broad interest from the scientific community because of the associated cost-effectiveness and easy access. In this review, we systematically and comprehensively summarize the natural products, including terpenoids, phenols, and alkaloids, among others, and the plant-derived crude extracts, that have been reported to ameliorate fibrosis via inhibiting NLRP3 inflammasome activation and highlight the underlying mechanisms. Among all the compounds, diterpenoids is the most promising candidates for inhibiting NLRP3 inflammasome activation and improving fibrosis, as they possess combined inhibitory effect on NLRP3 inflammasome assembly and NF-κB signaling pathway. All the information may aid in the development of therapeutic strategies for the treatment of fibrotic diseases.

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“…Among these complicated networks of molecular pathway, induction of oxidative stress is an early key mechanism of peritoneal EMT [52][53][54]. A major source of ROS in MCs is NADPH oxidase (NOX), mitochondrial electron transport, xanthine oxidase, and nitric oxide synthase.…”

Section: Mechanism Of Emtmentioning

confidence: 99%

Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis

Kang

2020

Kidney Res Clin Pract

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Phenotype transition of peritoneal mesothelial cells (MCs) including the epithelial-to-mesenchymal transition (EMT) is regarded as an early mechanism of peritoneal dysfunction and fibrosis in peritoneal dialysis (PD), producing proinflammatory and pro-fibrotic milieu in the intra-peritoneal cavity. Loosening of intercellular tight adhesion between adjacent MCs as an initial process of EMT creates the environment where mesothelium and submesothelial tissue are more vulnerable to the composition of bio-incompatible dialysates, reactive oxygen species, and inflammatory cytokines. In addition, down-regulation of epithelial cell markers such as E-cadherin facilitates de novo acquisition of mesenchymal phenotypes in MCs and production of extracellular matrices. Major mechanisms underlying the EMT of MCs include induction of oxidative stress, pro-inflammatory cytokines, endoplasmic reticulum stress and activation of the local renin-angiotensin system. Another mechanism of peritoneal EMT is mitigation of intrinsic defense mechanisms such as the peritoneal antioxidant system and anti-fibrotic peptide production in the peritoneal cavity. In addition to use of less bio-incompatible dialysates and optimum treatment of peritonitis in PD, therapies to prevent or alleviate peritoneal EMT have demonstrated a favorable effect on peritoneal function and structure, suggesting that EMT can be an early interventional target to preserve peritoneal integrity.

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Inhibition of IL-18 reduces renal fibrosis after ischemia-reperfusion

Cited by 42 publications

References 34 publications

Paricalcitol attenuates TGF‐β1–induced phenotype transition of human peritoneal mesothelial cells (HPMCs)viamodulation of oxidative stress and NLRP3 inflammasome

Paricalcitol attenuates TGF‐β1–induced phenotype transition of human peritoneal mesothelial cells (HPMCs)viamodulation of oxidative stress and NLRP3 inflammasome

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis

Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis

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