The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

Karlstetter, Marcus; Walczak, Yana; Weigelt, Karin; Ebert, Stefanie; Brülle, Jan; Schwer, Heinz; Fuchshofer, Rudolf; Langmann, Thomas

doi:10.4049/jimmunol.0903300

Cited by 64 publications

(58 citation statements)

References 70 publications

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“…Moreover, they demonstrated that AMWAP expression is rapidly induced by ligands for TLR2, -4, and -9 and IFN-g, thereby reducing proinflammatory cytokine expression (Karlstetter et al, 2010b).…”

Section: Microglia In Degenerating Diseasesmentioning

confidence: 99%

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Cuenca

Fernández‐Sánchez

Campello

et al. 2014

Progress in Retinal and Eye Research

344

394

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Section: Microglia In Degenerating Diseasesmentioning

confidence: 99%

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Cuenca

Fernández‐Sánchez

Campello

et al. 2014

Progress in Retinal and Eye Research

344

394

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“…We have previously characterized the macrophage/microglia WAP domain protein (AMWAP) as a regulator of pro-inflammatory response 37,38 . AMWAP transcription is rapidly induced in microglia from different retinal disease mouse models, including inherited photoreceptor dystrophies and different light challenge paradigms 7,32,33,39 .…”

Section: Development Of the Protocolmentioning

confidence: 99%

Comprehensive analysis of mouse retinal mononuclear phagocytes

et al. 2017

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“…AMWAP was recently identified as a counter-regulator of the proinflammatory response in macrophages. 36 However, its role in diabetes or any other disease has never been examined. Figure 8L).…”

Section: Il-17a Administration Suppresses Podocyte and Tubular Epithementioning

confidence: 99%

“…However, AMWAP significantly reduced albuminuria and glomerulosclerosis (Figure 9, E-G). Because AMWAP is known to have anti-inflammatory activity 36 by turning macrophages to the M2 phenotype, we analyzed M2 marker expression in vehicle-and AMWAP-treated control and diabetic mouse kidney. Vehicle-treated diabetic mouse kidney showed increased proinflammatory M1 marker (IL-6 and IL-1b) ( Epithelial Cell-Specific Overexpression of IL-17A or IL-17F Is Sufficient to Suppress Diabetic Nephropathy in Mice We have created IL-17A and IL-17F overexpressing mice using the epithelial cellspecific E-cadherin promoter.…”

Section: Il-17a Administration Suppresses Podocyte and Tubular Epithementioning

confidence: 99%

Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis

Mohamed

Jayakumar

Chen

et al. 2016

Journal of the American Society of Nephrology

105

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Diabetes is the leading cause of kidney failure, accounting for .45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinasedependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease. CKDs such as diabetic nephropathy are a serious public health problem. In the United States, .20 million adults have CKD, and 20%-40% of patients with diabetes develop nephropathy. The financial burden of diabetes is estimated to be $245 billion per year in the United States alone, and the cost for diabetic nephropathy is estimated to be .$20 billion per year. While intensive insulin therapy and control of hypertension can delay the onset of diabetic nephropathy, 1-3 these therapies cannot reverse CKD once it has developed. Recently, feeding mice a strictly ketogenic diet (5% carbohydrate, 8% protein, 87% fat) reversed a mild form of nephropathy. 4 Although implementing such an extreme diet

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The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

Abstract: Material

Cited by 64 publications

References 70 publications

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Comprehensive analysis of mouse retinal mononuclear phagocytes

Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis

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