Role of interleukin-1 in mesangial cell proliferation and matrix deposition in experimental mesangioproliferative nephritis.
We examined the functional role of interleukin (IL)-1 in mesangial cell proliferation during rat anti-Thy-1 nephritis by blocking its action with IL-1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was induced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred Wistar rats. Groups of animals (n = 9) were implanted with a micro-osmotic pump on day -1, which delivered 25 micrograms/hour human recombinant IL-1ra or saline continuously until the rats were killed at day 6, the peak of mesangial cell proliferation. Immunostaining showed that IL-1 was expressed by mesangial cells during disease. IL-1ra treatment did not affect the mild, but significant, proteinuria seen after OX-7 injection. Compared with saline treatment, IL-1ra treatment reduced mesangial cell proliferation (decreases 24% P < 0.05), glomerular hypercellularity (decreases 29%; P < 0.05), and glomerular macrophage accumulation (decreases 20%; P < 0.05). However, IL-1ra treatment had no effect on glomerular IL-1 beta mRNA expression and caused only a small reduction in the high levels of glomerular expression of platelet-derived growth factor-beta protein (decreases 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transforming growth factor-beta 1 mRNA expression on day 6 (decreases 26%; P < 0.05), although urinary excretion of this factor was unaffected. Interestingly, IL-1ra treatment had relatively little effect upon glomerular deposition of laminin, fibronectin, and collagen type IV seen in this acute disease. In conclusion, this study has 1) demonstrated that IL-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferative nephritis, and 3) suggests that IL-1 has little or no fibrogenic activity in mesangial matrix deposition.
Tesch
G H
GH
Department of Nephrology, Monash Medical Centre, Clayton Victoria, Australia.
Lan
H Y
HY
Atkins
R C
RC
Nikolic-Paterson
D J
DJ
D000818:Animals; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology*; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology*; D006133:Growth Substances / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology*; D007518:Isoantibodies / Q000633:toxicity; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000627:therapeutic use; D018800:Thy-1 Antigens / Q000276:immunology
D006133:Growth Substances; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007518:Isoantibodies; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D018800:Thy-1 Antigens; C035678:anti-Thy antibody