HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/F703    most recent 00254.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Qi, W. Articles by Pollock, C. A. Search for Related Content PubMed PubMed Citation Articles by Qi, W. Articles by Pollock, C. A.

TGF-₁ induces IL-8 and MCP-1 through a connective tissue growth factor-independent pathway

¹Department of Medicine, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney; ²Department of Medicine, University of Sydney, and Royal Prince Alfred Hospital, Sydney; and ³Department of Medicine, St. Vincent's Hospital, Melbourne, Australia, and Department of Medicine, University of Toronto, St. Michael's Hospital, Toronto, Ontario, Canada

Submitted 20 June 2005 ; accepted in final form 28 September 2005

Transforming growth factor-₁ (TGF-₁) functions as an important immunomodulatory cytokine in human kidney. Evidence suggests that connective tissue growth factor (CTGF) is an important downstream mediator of the profibrotic effects of TGF-₁. However, the role of CTGF in TGF-₁-induced chemokine production remains unknown. This study was undertaken to determine whether CTGF is involved in mediating TGF-₁-induced chemokine production in renal proximal tubular (HK-2) cells. Interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured. TGF-₁ induced an increase in IL-8 and MCP-1 (both P < 0.05) compared with control levels. CTGF was effectively silenced using small interference RNA (siRNA) in HK-2 cells. RT-PCR and real-time PCR confirmed a 94% reduction in CTGF mRNA. In the CTGF-silenced cells, TGF-₁-stimulated IL-8 and MCP-1 secretion was not altered compared with control cells. Similarly, basal secretion of IL-8 and MCP-1 was not changed in CTGF-silenced cells. The direct effect of CTGF (20, 200, and 400 ng/ml) on IL-8 and MCP-1 was assessed at 24-, 48-, and 72-h time points and no stimulation was observed. Our studies further demonstrate that in the CTGF gene-silenced cells, CTGF partially mediates TGF-₁-induced fibronectin and collagen IV secretion. These data suggest that TGF-₁ induced IL-8 and MCP-1 via CTGF-independent pathway. TGF- mediates both fibrosis and chemokine production in the proximal tubule of the kidney. However, CTGF plays a more specific role as a downstream mediator of TGF-₁-induced fibrosis.

small interference RNA; fibronectin; collagen IV

This article has been cited by other articles:

				J. Park, D.-R. Ryu, J. J. Li, D.-S. Jung, S.-J. Kwak, S. H. Lee, T.-H. Yoo, S. H. Han, J. E. Lee, D. K. Kim, et al. MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells Am J Physiol Renal Physiol, September 1, 2008; 295(3): F749 - F757. [Abstract] [Full Text] [PDF]

				W. Qi, X. Chen, J. Holian, E. Mreich, S. Twigg, R. E. Gilbert, and C. A. Pollock Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells Am J Physiol Renal Physiol, November 1, 2006; 291(5): F1070 - F1077. [Abstract] [Full Text] [PDF]