IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis.
BACKGROUND: IL-1beta has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or by effects mediated through tubular cell transforming growth factor (TGF)-beta production, previously demonstrated in vitro. METHODS: The in vivo roles of endogenous IL...
| Váldodahkkit: | , , , , , , , , |
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| Materiálatiipa: | Journal article |
| Giella: | English |
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2009
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| _version_ | 1826290773327347712 |
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| author | Jones, L O'Sullivan, K Semple, T Kuligowski, M Fukami, K Ma, F Nikolic-Paterson, D Holdsworth, SR Kitching, A |
| author_facet | Jones, L O'Sullivan, K Semple, T Kuligowski, M Fukami, K Ma, F Nikolic-Paterson, D Holdsworth, SR Kitching, A |
| author_sort | Jones, L |
| collection | OXFORD |
| description | BACKGROUND: IL-1beta has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or by effects mediated through tubular cell transforming growth factor (TGF)-beta production, previously demonstrated in vitro. METHODS: The in vivo roles of endogenous IL-1beta and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL/6 mice, IL-1beta(-/-) and IL-1RI(-/-) mice with unilateral ureteric obstruction. RESULTS: After 7 days, IL-1RI(-/-) mice (IL-1alpha and IL-1beta deficient) were protected from injury and collagen accumulation. IL-1beta(-/-) mice demonstrated some histological protection, but no reduction in alpha1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-beta1 mRNA was reduced in IL-1RI(-/-) mice (with trends to reduced TGF-beta2 and TGF-beta3). Expression of a downstream TGF-beta effector, connective tissue growth factor, was decreased in IL-1RI(-/-) mice. IL-1RI(-/-) mice exhibited less tubulointerstitial apoptosis compared with wild-type mice. Macrophage infiltration and adhesion molecule mRNA expression was unchanged in IL-1beta(-/-) or IL-1RI(-/-) mice. While TNF expression was similar to wild-type mice, IFN-gamma expression was reduced in both IL-1beta(-/-) and IL-1RI(-/-) mice. IL-1RI(-/-) mice at 14 days showed a catch-up in fibrosis compared with wild-type mice. CONCLUSION: IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI(-/-) mice were more protected at an early stage, associated with changes in TGF-beta and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages. |
| first_indexed | 2024-03-07T02:49:19Z |
| format | Journal article |
| id | oxford-uuid:ad1ee3ef-df18-4f50-91f6-1c4fce6fe7c7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:49:19Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:ad1ee3ef-df18-4f50-91f6-1c4fce6fe7c72022-03-27T03:33:26ZIL-1RI deficiency ameliorates early experimental renal interstitial fibrosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ad1ee3ef-df18-4f50-91f6-1c4fce6fe7c7EnglishSymplectic Elements at Oxford2009Jones, LO'Sullivan, KSemple, TKuligowski, MFukami, KMa, FNikolic-Paterson, DHoldsworth, SRKitching, A BACKGROUND: IL-1beta has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or by effects mediated through tubular cell transforming growth factor (TGF)-beta production, previously demonstrated in vitro. METHODS: The in vivo roles of endogenous IL-1beta and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL/6 mice, IL-1beta(-/-) and IL-1RI(-/-) mice with unilateral ureteric obstruction. RESULTS: After 7 days, IL-1RI(-/-) mice (IL-1alpha and IL-1beta deficient) were protected from injury and collagen accumulation. IL-1beta(-/-) mice demonstrated some histological protection, but no reduction in alpha1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-beta1 mRNA was reduced in IL-1RI(-/-) mice (with trends to reduced TGF-beta2 and TGF-beta3). Expression of a downstream TGF-beta effector, connective tissue growth factor, was decreased in IL-1RI(-/-) mice. IL-1RI(-/-) mice exhibited less tubulointerstitial apoptosis compared with wild-type mice. Macrophage infiltration and adhesion molecule mRNA expression was unchanged in IL-1beta(-/-) or IL-1RI(-/-) mice. While TNF expression was similar to wild-type mice, IFN-gamma expression was reduced in both IL-1beta(-/-) and IL-1RI(-/-) mice. IL-1RI(-/-) mice at 14 days showed a catch-up in fibrosis compared with wild-type mice. CONCLUSION: IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI(-/-) mice were more protected at an early stage, associated with changes in TGF-beta and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages. |
| spellingShingle | Jones, L O'Sullivan, K Semple, T Kuligowski, M Fukami, K Ma, F Nikolic-Paterson, D Holdsworth, SR Kitching, A IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title | IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title_full | IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title_fullStr | IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title_full_unstemmed | IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title_short | IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. |
| title_sort | il 1ri deficiency ameliorates early experimental renal interstitial fibrosis |
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