Effect of IL-11 on glomerular expression of TGF-beta and extracellular matrix in nephrotoxic nephritis in Wistar Kyoto rats.
BACKGROUND
The effect of interleukin-11 (IL-11) on transforming growth factor-ß (TGF-ß) is controversial and has not been examined in renal diseases. In this study, we (i) characterised the up-regulation of TGF-ß1, phospho-p38 MAPK (p-p38 MAPK) and extracellular matrix during pathogenesis of glomerulonephritis and (ii) examined the effect of rhIL-11 on these processes in vivo.


METHODS
Following induction of nephrotoxic nephritis, expression of TGF-ß1, alpha-smooth muscle actin (alpha-SMA), fibronectin and p-p38 MAPK was detected in the kidney. Rats were treated either with vehicle or rhIL-11 at a high or low dose and culled on day 6.


RESULTS
A high dose of rhIL-11 resulted in a significant reduction in the glomerular expression of TGF-ß1 (0.4 ± 0.1 vs. 2.04 ± 0.4 semiquantitative score, p<0.005), alpha-SMA (0.6 ± 0.2 vs. 1.5 ± 0.3, p<0.01) and fibronectin (0.6 ± 0.1 vs. 1.5 ± 0.1, p<0.02). The periglomerular expression of alpha-SMA and fibronectin was significantly reduced in rats treated with the high dose of rhIL-11 (9.6% ± 2% vs. 92% ± 2.5% of glomeruli, p<0.01; and 26% ± 4.9% vs. 94% ± 1.9% of glomeruli, p<0.005, respectively). There was a slight but insignificant reduction of p-p38 MAPK in IL-11 treated rats. Treatment with low-dose rhIL-11 did not reduce expression of these molecules.


CONCLUSIONS
IL-11 suppresses glomerular expression of TGF-ß1 and extracellular matrix deposition in experimental glomerulonephritis.
Stangou
Maria
M
Imperial College Kidney and Transplant Institute, Division of Medicine, Imperial College London, London, UK. Victoria.a.kumar@kp.org
Bhangal
Gurjeet
G
Lai
Ping-Chin
PC
Smith
Jennifer
J
Keith
James C
JC
Boyle
Joseph J
JJ
Pusey
Charles D
CD
Cook
Terence
T
Tam
Frederick W K
FW
D000199:Actins / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000199:Actins; D001323:Autoantibodies; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017370:Interleukin-11; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C508611:IL11 protein, human; C508962:Tgfb1 protein, rat; C051951:antiglomerular basement membrane antibody; C498862:Acta2 protein, rat