Interleukin-1 beta stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-beta-dependent mechanism

Vesey, David A., Cheung, Catherine, Cuttle, Leila, Endre, Zoltan, Gobe, Glenda and Johnson, David W. (2002) Interleukin-1 beta stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-beta-dependent mechanism. Journal of Laboratory And Clinical Medicine, 140 5: 342-350. doi:10.1067/mlc.2002.128468


Author Vesey, David A.
Cheung, Catherine
Cuttle, Leila
Endre, Zoltan
Gobe, Glenda
Johnson, David W.
Title Interleukin-1 beta stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-beta-dependent mechanism
Formatted title
Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism
Journal name Journal of Laboratory And Clinical Medicine   Check publisher's open access policy
ISSN 0022-2143
Publication date 2002-11-01
Sub-type Article (original research)
DOI 10.1067/mlc.2002.128468
Volume 140
Issue 5
Start page 342
End page 350
Total pages 9
Place of publication St Louis, USA
Publisher Mosby
Language eng
Subject C1
730118 Organs, diseases and abnormal conditions not elsewhere classified
110312 Nephrology and Urology
Formatted abstract
One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1β (IL-1β), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1β. We found that IL-1β significantly stimulated DNA synthesis (356.7% ± 39% of control, P < .003), fibronectin secretion (261.8 ± 11% of control, P < .005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% ± 26% of control, P < .005), transforming growth factor-β (TGF-β) secretion (211% ± 37% of control, P < .01), and nitric oxide (NO) production (342.8% ± 69% of control, P < .002). TGF-β (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1β. Neither a NO synthase inhibitor (NG-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 μmol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1β treatment. However, addition of a TGF-β-neutralizing antibody significantly reduced IL-1β-induced fibronectin secretion (IL-1β + IgG, 262% ± 72% vs IL-1β + αTGF-β 156% ± 14%, P < .02), collagen type 1 production (IL-1β + IgG, 176% ± 28% vs IL-1β + αTGF-β, 120% ± 14%, P < .005) and abrogated IL-1β-induced DNA synthesis (245% ± 49% vs 105% ± 21%, P < .005). IL-1β significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFβ, and NO. The fibrogenic and proliferative action of IL-1β on CF appears not to involve activation of PKC or production of NO but is at least partly TGFβ-dependent. (J Lab Clin Med 2002;140:342-50)
Keyword Medical Laboratory Technology
Medicine, General & Internal
Medicine, Research & Experimental
Tumor-necrosis-factor
Proximal Tubule Cells
Nitric-oxide
Mesangial Cells
Kinase-c
Factor-alpha
Collagen-synthesis
Epithelial-cells
Angiotensin-ii
Pathogenesis
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 03:48:41 EST