| Autor: |
Hy, Lan, Jm, Fan, Xr, Huang, Yy, Ng, Dj, Nikolic-Paterson, W, Mu, RC., Atkins |
| Předmět: |
|
| Zdroj: |
Nephrology; Oct2000, Vol. 5 Issue 3, pA101, 1p |
| Abstrakt: |
We have previously shown that blocking of IL-1 with the IL-1ra inhibited tubulointerstitial fibrosis in rat anti-GBM glomerulonephritis. Recently, we have also demonstrated that tubular epithelial cells (TEC) are pro-fibrogenitor cells capable of TEMT in progressive renal fibrosis in remnant kidney and anti-GBM rat models. This study investigated whether IL-1 can induce TEMT in vitro. A characterised normal rat kidney epithelial cell line (NRKE52) was cultured either in plastic dishes or slides coated with collagen gel (collagen type I) and were grown in DMEM medium containing 1% FCS until sub-confluence, rmIL-1α at doses 0, 1, 10, 20ng/ml with or without IL-1ra (20ug/ml) or a neutralising anti-TGF-β antibody (10ng/ml) was added into the cells and cultured for 5 days. TEMT was determined by Northern and Western blotting, flow cytometry, and immunohistochemistry with alpha smooth muscle actin (α-SMA) expression or examined by scanning electron microscopy. There were three novel findings from this study: (1) NRKE52 cells cultured with medium (i%FCS) alone caused no evidence of TEMT. However, marked expression of α-SMA mRNA and protein with the loss of TEC morphology was found in the cells cultured with IL-1α, accounting for 20-25% of total TEC; (2) There was dose dependent effect for IL-1α on regulating TEMT and this was completely abrogated by the IL-1ra; (3) IL-1α-induced TEMT was significantly inhibited by the anti-TGF-β antibody (70%,↓). In conclusion, we have demonstrated that IL-1 can induce TEMT directly or indirectly through TGF-β dependent mechanism in vitro. ILl-induced TEMT may be one mechanism by which IL-1 plays a role in renal fibrosis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
