Interleukin‐17A participates in podocyte injury by inducing <scp>IL</scp>‐1β secretion through <scp>ROS</scp>‐<scp>NLRP</scp>3 inflammasome‐caspase‐1 pathway

Yan, Jingye; Li, Y.; Yang, Haiping; Zhang, L.; Yang, Bo; Wang, M.; Li, Q.

doi:10.1111/sji.12645

Cited by 40 publications

(23 citation statements)

References 25 publications

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“…The role of IL-6 in podocyte pathogenesis has been shown previously, where high glucose and IL-6 stimulation led to podocyte hypertrophy, which was attenuated by anti-IL-6-neutralizing antibodies [20]. Similarly, other cytokines such as IL17A, interferon (IFN)-α, and IFN-β were found to be involved in glomerulosclerosis [21,22]. Studies further indicate that podocytes possess components of innate immunity and their induction may contribute to podocyte injury and podocytopathies [23].…”

Section: Discussionmentioning

confidence: 63%

The Use of High-Throughput Transcriptomics to Identify Pathways with Therapeutic Significance in Podocytes

Solanki

Srivastava

Rahman

et al. 2019

IJMS

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Podocytes have a unique structure that supports glomerular filtration function, and many glomerular diseases result in loss of this structure, leading to podocyte dysfunction and ESRD (end stage renal disease). These structural and functional changes involve a complex set of molecular and cellular mechanisms that remain poorly understood. To understand the molecular signature of podocyte injury, we performed transcriptome analysis of cultured human podocytes injured either with PAN (puromycin aminonucleoside) or doxorubicin/adriamycin (ADR). The pathway analysis through DE (differential expression) and gene-enrichment analysis of the injured podocytes showed Tumor protein p53 (P53) as one of the major signaling pathways that was significantly upregulated upon podocyte injury. Accordingly, P53 expression was also up-regulated in the glomeruli of nephrotoxic serum (NTS) and ADR-injured mice. To further confirm these observations, cultured podocytes were treated with the P53 inhibitor pifithrin-α, which showed significant protection from ADR-induced actin cytoskeleton damage. In conclusion, signaling pathways that are involved in podocyte pathogenesis and can be therapeutically targeted were identified by high-throughput transcriptomic analysis of injured podocytes.

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Section: Discussionmentioning

confidence: 63%

The Use of High-Throughput Transcriptomics to Identify Pathways with Therapeutic Significance in Podocytes

Solanki

Srivastava

Rahman

et al. 2019

IJMS

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“…Studies have linked IL-17 signalling with promotion of podocyte injury in both primary nephrotic syndrome and adriamycin-induced nephropathy 39,40 . Stimulation of podocytes with rIL-17 in vitro induced inflammation and apoptosis through secretion of IL-1β and activation of the NLRP3 inflammasome 41 . In our study, primary cultures of podocytes displayed up-regulated expression of pro-inflammatory cytokines and chemokines in response to high glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 17A promotes diabetic kidney injury

Chen

et al. 2019

Sci Rep

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The role of the pro-inflammatory cytokine IL-17 in the pathogenesis of numerous inflammatory disorders is well-documented, but conflicting results are reported for its role in diabetic nephropathy. Here we examined the role of IL-17 signalling in a model of streptozotocin-induced diabetic nephropathy through IL-17 knockout mice, administration of neutralising monoclonal anti-IL-17 antibody and in vitro examination of gene expression of renal tubular cells and podocytes under high glucose conditions with or without recombinant IL-17. IL-17 deficient mice were protected against progression of diabetic nephropathy, exhibiting reduced albuminuria, glomerular damage, macrophage accumulation and renal fibrosis at 12 weeks and 24 weeks. Administration of anti-IL-17 monoclonal antibody to diabetic wild-type mice was similarly protective. IL-17 deficiency also attenuated up-regulation of pro-inflammatory and pro-fibrotic genes including IL-6, TNF-α, CCL2, CXCL10 and TGF-β in diabetic kidneys. In vitro co-stimulation with recombinant IL-17 and high glucose were synergistic in increasing the expression of pro-inflammatory genes in both cultured renal tubular cells and podocytes. We conclude that absence of IL-17 signalling is protective against streptozotocin-induced diabetic nephropathy, thus implying a pro-inflammatory role of IL-17 in its pathogenesis. Targeting the IL-17 axis may represent a novel therapeutic approach in the treatment of this disorder.

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“…Since IL-17 synthesis is induced by IL-23 ( 30 ) and IL-17-induced effect can use inflammasome-caspase-1 pathway ( 31 ), we next investigated changes in the expression of IL-23A and caspase-1 after stimulation with the 6 different S . Typhi strains by qRT-PCR.…”

Section: Resultsmentioning

confidence: 99%

Manipulation of Salmonella Typhi Gene Expression Impacts Innate Cell Responses in the Human Intestinal Mucosa

et al. 2018

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Although immunity induced by typhoid fever is moderated and short-lived, typhoid vaccination with the attenuated Ty21a oral vaccine generates long-lasting protection rates reaching up to 92%. Thus, there are important differences on how wild-type Salmonella and typhoid vaccine strains stimulate host immunity. We hypothesize that vaccine strains with different mutations might affect gut inflammation and intestinal permeability by different mechanisms. To test this hypothesis, we used an in vitro organotypic model of the human intestinal mucosa composed of human intestinal epithelial cells, lymphocytes/monocytes, endothelial cells, and fibroblasts. We also used six Salmonella enterica serovar Typhi (S. Typhi) strains: the licensed Ty21a oral vaccine, four typhoid vaccine candidates (i.e., CVD 908, CVD 909, CVD 910, and CVD 915) and the wild-type Ty2 strain. We found that genetically engineered S. Typhi vaccine strains elicit differential host changes not only in the intestinal permeability and secretion of inflammatory cytokines, but also in the phenotype and activation pathways of innate cells. These changes were distinct from those elicited by the parent wild-type S. Typhi and depended on the genetic manipulation. In sum, these results emphasize the importance of carefully selecting specific manipulations of the Salmonella genome in the development of typhoid vaccines.

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Interleukin‐17A participates in podocyte injury by inducing IL‐1β secretion through ROS‐NLRP3 inflammasome‐caspase‐1 pathway

Cited by 40 publications

References 25 publications

The Use of High-Throughput Transcriptomics to Identify Pathways with Therapeutic Significance in Podocytes

The Use of High-Throughput Transcriptomics to Identify Pathways with Therapeutic Significance in Podocytes

Interleukin 17A promotes diabetic kidney injury

Manipulation of Salmonella Typhi Gene Expression Impacts Innate Cell Responses in the Human Intestinal Mucosa

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