Suppression of experimental crescentic glomerulonephritis by interleukin-10 gene transfer
| Autor: | Adel Galal El-Shemi, Tadashi Yamamoto, Zhenyun Qu, Ignacio Anegon, Goro Nishimoto, Eishin Yaoita, Asako Matsuki, Hidehiko Fujinaka, Vladimir Bilim, Yuatka Yoshida, Pavel Kovalenko, Junichi Kamiie |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
interleukin-1β Anti-Glomerular Basement Membrane Disease Genetic Vectors Kidney Glomerulus Gene Expression macrophage CD8+ T cells urologic and male genital diseases Rats Inbred WKY Adenoviridae Blood Urea Nitrogen Internal medicine Gene expression medicine Animals Cytotoxic T cell RNA Messenger gene transfer biology urogenital system Gene Transfer Techniques Histology Glomerulonephritis a-GBM glomerulonephritis medicine.disease Immunohistochemistry female genital diseases and pregnancy complications Interleukin-10 Rats Proteinuria Interleukin 10 inteleukin-10 Endocrinology Nephrology Creatinine Disease Progression biology.protein Female Lymph Nodes Antibody Spleen CD8 Interleukin-1 |
| Zdroj: | Kidney International. 65:1280-1289 |
| ISSN: | 0085-2538 |
| DOI: | 10.1111/j.1523-1755.2004.00536.x |
| Popis: | Suppression of experimental crescentic glomerulonephritis by interleukin-10 gene transfer.BackgroundInvestigated were effects of overexpression of interleukin-10 (IL-10) on the outcome and progression of crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats.MethodsRats were singly or simultaneously injected with antiglomerular basement membrane (a-GBM) antibody and adenoviral vector encoding rat IL-10 (Ad-rIL-10) or LacZ (Ad-LacZ) (3 × 1010 pfu/rat) intravenously, and were sacrificed at day 7. Their kidneys and other organs were isolated and examined by histology and immunohistochemistry. The In vivo expression of IL-10 mRNA in the liver of Ad-rIL-10–injected rats was confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assay analysis and its translated protein was measured in the serum by enzyme-linked immunosorbent assay (ELISA).ResultsThe exogenous IL-10 mRNA was strongly expressed in the liver in a dose-dependent manner and was intense at days 4 and 7 but was less intense at day 14. Ad-rIL-10 treatment significantly reduced the incidence of glomerular crescent formation from 67%± 1.9% in a-GBM antibody–treated group or 69.8%± 1.9% in a-GBM antibody + Ad-LacZ–treated group to 21.6%± 1.8% (P < 0.001), the glomerular infiltration of macrophages from 35.7 ± 6.3 cell s/gcs (a-GBM antibody) or 37.6 ± 8.6 cells/gcs (both a-GBM antibody + Ad-LacZ) to 17.9 ± 5.5 cells/gcs (P < 0.001), that of major histocompatibility complex (MHC) class II–positive cells from 14.4 ± 5.3 cells/gcs (a-GBM antibody) or 15 ± 4.6 cells/gcs (a-GBM antibody + Ad-LacZ) to 5.7 ± 2.3 cells/gcs (P < 0.0001) at day 7, the glomerular and immune tissue expression of IL-1β mRNA, as well as the proteinuria from 159.0 ± 22.7mg/24hours (a-GBM antibody) or 166 ± 28mg/24hours (a-GBM antibody + Ad-LacZ) to 42.2 ± 35.2mg/24hours (P < 0.01) at day 7. The serum creatinine and blood urea nitrogen levels were also reduced from 2.8 ± 0.1mg/dL (a-GBM antibody) or 2.8 ± 0.1mg/dL (a-GBM antibody + Ad-LacZ) to 1.0 ± 0.1mg/dL (P < 0.001) and from 63.2 ± 8.9mg/dL (a-GBM antibody) or 61.3 ± 5.2mg/dL (a-GBM antibody + Ad-LacZ) to 27.0 ± 4.5mg/dL (P < 0.001), respectively. However, the glomerular accumulation of CD8+ T cells was unaffected: 5.4 ± 1.1 cells/gcs (a-GBM antibody + Ad-rIL-10), 5.9 ± 1.5 cells/gcs (a-GBM antibody), and 5.8 ± 1.1 cells/gcs (a-GBM antibody + Ad-LacZ) (P = NS).ConclusionIL-10 gene transfer significantly attenuated the glomerular lesions and injury in the anti-GBM crescentic glomerulonephritis of WKY rats. |
| Databáze: | OpenAIRE |
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