Dataset Information

TNFR2 interposes the proliferative and NF-?B-mediated inflammatory response by podocytes to TNF-?.

ABSTRACT: The development of proliferative podocytopathies has been linked to ligation of tumor necrosis factor receptor 2 (TNFR2) expressed on the renal parenchyma; however, the TNFR2-positive cells within the kidney responsible for podocyte injury are unknown. We detected de novo expression of TNFR2 on podocytes before hyperplastic injury in crescentic glomerulonephritis of mice with nephrotoxic nephritis, and in collapsing glomerulopathy of Tg26(HIV/nl) mice, kd/kd mice, and human beings. We further found that serum levels of soluble TNF-? and TNFR2 correlated significantly with renal injury in Tg26(HIV/nl) mice. Thus, we asked whether ligand binding of TNFR2 on podocytes ex vivo precipitates the characteristic proliferative and pro-inflammatory diseased podocyte phenotypes. Soluble TNF-? activated NF-?B and dose-dependently induced podocyte proliferation, marked by the expression of the podocyte G(1) cyclin and NF-?B target gene, cyclin D1. Microarray gene and chemokine protein expression profiling showed a marked pro-inflammatory NF-?B signature, and activated podocytes secreting CCL2- and CCL5-induced macrophage migration in transwell assays. Neutralization of TNFR2 on podocytes with blocking antibodies abrogated NF-?B activation and the induction of cyclin D1 by TNF-?, and identified TNFR2 as the primary receptor that induced I?B? degradation, the initiating event in NF-?B activation. These results suggest that TNFR2 expressed on podocytes and its canonical NF-?B signaling may directly interpose the compound pathogenic responses by podocytes to TNF-?, in the absence of other TNFR2-positive renal cell types in proliferative podocytopathies.

SUBMITTER: Bruggeman LA

PROVIDER: S-EPMC3075956 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TNFR2 interposes the proliferative and NF-κB-mediated inflammatory response by podocytes to TNF-α.

Bruggeman Leslie A LA Drawz Paul E PE Kahoud Nicole N Lin Ke K Barisoni Laura L Nelson Peter J PJ

Laboratory investigation; a journal of technical methods and pathology 20110110 3

The development of proliferative podocytopathies has been linked to ligation of tumor necrosis factor receptor 2 (TNFR2) expressed on the renal parenchyma; however, the TNFR2-positive cells within the kidney responsible for podocyte injury are unknown. We detected de novo expression of TNFR2 on podocytes before hyperplastic injury in crescentic glomerulonephritis of mice with nephrotoxic nephritis, and in collapsing glomerulopathy of Tg26(HIV/nl) mice, kd/kd mice, and human beings. We further fo ...[more]

PMID: 21221075

Similar Datasets

Project description:Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence β-galactosidase staining was used to detect the activity levels of β-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1β and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.

Dataset Information

TNFR2 interposes the proliferative and NF-?B-mediated inflammatory response by podocytes to TNF-?.

Publications

TNFR2 interposes the proliferative and NF-κB-mediated inflammatory response by podocytes to TNF-α.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets