Abstract
Macrophages are intimately involved in the development of immune-mediated inflammation, including glomerulonephritis. We have transduced primary cultures of macrophages to express IL-10 and tested the ability of these cells to control rat nephrotoxic nephritis (NTN), a model of human glomerulonephritis. Ad-IL-10-transduced bone-marrow-derived macrophages (BMDM) produced large amounts of IL-10 in culture, and their TNF-alpha production was decreased in response to interferon-gamma and LPS. Transduced macrophages were injected into the renal artery of rats, 6 h after the induction of NTN, where they localized efficiently to inflamed rat glomeruli. Delivery of IL-10-expressing macrophages to nephritic rats produced a marked reduction in albuminuria compared with unmodified NTN or injection of Ad-null-transduced BMDM. IL-10 treatment decreased the number of glomerular ED1- and ED3-positive cells, MHC class 11 expression, and the number of fibrinoid lesions. Interestingly, anti-inflammatory changes in the Ad-IL10-injected kidney were mirrored by changes in the contralateral kidney. These results highlight that Ad-IL-10-transduced macrophages infiltrate inflamed glomeruli and reduce the severity of glomerular inflammation, emphasizing the value of local delivery of genetically modified macrophages in the manipulation of inflammatory disease.
Original language | English |
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Pages (from-to) | 710-717 |
Number of pages | 8 |
Journal | Molecular Therapy |
Volume | 6 |
DOIs | |
Publication status | Published - 2002 |
Keywords
- macrophage
- gene therapy
- IL-10
- nephrotoxic nephritis
- inflammation
- autoimmunity
- adenovirus
- contralateral effect
- COLLAGEN-INDUCED ARTHRITIS
- CRESCENTIC GLOMERULONEPHRITIS
- GENE-TRANSFER
- DENDRITIC CELLS
- RABBIT KNEES
- VIRAL IL-10
- T-CELLS
- INTERLEUKIN-10
- DISEASE
- EXPRESSION