IL-17 Expression in the Time Course of Acute Anti-Thy1 Glomerulonephritis.

Abstract

BACKGROUND:

Interleukin-17 (IL-17) is a new pro-inflammatory cytokine involved in immune response and inflammatory disease. The main source of IL-17 is a subset of CD4+ T-helper cells, but is also secreted by non-immune cells. The present study analyzes expression of IL-17 in the time course of acute anti-thy1 glomerulonephritis and the role of IL-17 as a potential link between inflammation and fibrosis.

METHODS:

Anti-thy1 glomerulonephritis was induced into male Wistar rats by OX-7 antibody injection. After that, samples were taken on days 1, 5, 10 (matrix expansion phase), 15 and 20 (resolution phase). PBS-injected animals served as controls. Proteinuria and histological matrixes score served as the main markers for disease severity. In in vitro experiments, NRK-52E cells were used. For cytokine expressions, mRNA and protein levels were analyzed by utilizing RT-PCR, in situ hybridization and immunofluorescence.

RESULTS:

Highest IL-17 mRNA-expression (6.50-fold vs. con; p<0.05) was found on day 5 after induction of anti-thy1 glomerulonephritis along the maximum levels of proteinuria (113 ± 13 mg/d; p<0.001), histological glomerular-matrix accumulation (82%; p<0.001) and TGF-β1 (2.2-fold; p<0.05), IL-6 mRNA expression (36-fold; p<0.05). IL-17 protein expression co-localized with the endothelial cell marker PECAM in immunofluorescence. In NRK-52E cells, co-administration of TGF-β1 and IL-6 synergistically up-regulated IL-17 mRNA 4986-fold (p<0.001).

CONCLUSIONS:

The pro-inflammatory cytokine IL-17 is up-regulated in endothelial cells during the time course of acute anti-thy1 glomerulonephritis. In vitro, NRK-52E cells secrete IL-17 under pro-fibrotic and pro-inflammatory conditions.

• Authors: Tanja Loof, Stephanie Krämer, Jens Gaedeke, Hans-Hellmut Neumayer, Harm Peters
• Journal: PloS one (PLoS One) Vol. 11 Issue 5 Pg. e0156480 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27243813 (Publication Type: Journal Article)

Chemical References

• Il17a protein, rat
• Interleukin-17
• Interleukin-6
• Isoantibodies
• RNA, Messenger
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• anti-Thy antibody

Topics

• Animals
• Cell Line
• Disease Models, Animal
• Glomerulonephritis (etiology, genetics, immunology)
• Interleukin-17 (genetics, metabolism)
• Interleukin-6 (administration & dosage, genetics)
• Isoantibodies (metabolism)
• Male
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Transforming Growth Factor beta1 (administration & dosage, genetics, metabolism)
• Up-Regulation