This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Witowski, J. Articles by Jörres, A. Search for Related Content PubMed PubMed Citation Articles by Witowski, J. Articles by Jörres, A.

(American Journal of Pathology. 2001;158:1441-1450.)
© 2001 American Society for Investigative Pathology

Regular Articles

Synthesis of C-X-C and C-C Chemokines by Human Peritoneal Fibroblasts

Induction by Macrophage-Derived Cytokines

Janusz Witowski^*, Annette Thiel^*, Ralf Dechend, Katharina Dunkel^*, Nina Fouquet^*, Thorsten O. Bender^*, Jan M. Langrehr, Gerhard M. Gahl^*, Ulrich Frei^* and Achim Jörres^*

From the Department of Nephrology and Medical Intensive Care,^*
the Department of Surgery,
Campus Virchow-Klinikum, and the Franz Volhard Klinik,
Campus Berlin-Buch, Medical Faculty Charité, Humboldt-Universität zu Berlin, Berlin, Germany

Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1ß and tumor necrosis factor-. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1ß as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1ß and tumor necrosis factor- produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-B binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein B- proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-B/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis.

This article has been cited by other articles:

				Y.-L. Shi, X.-Z. Luo, X.-Y. Zhu, K.-Q. Hua, Y. Zhu, and D.-J. Li Effects of combined 17beta-estradiol with TCDD on secretion of chemokine IL-8 and expression of its receptor CXCR1 in endometriotic focus-associated cells in co-culture Hum. Reprod., April 1, 2006; 21(4): 870 - 879. [Abstract] [Full Text] [PDF]

				S. Kato, Y. Yuzawa, N. Tsuboi, S. Maruyama, Y. Morita, T. Matsuguchi, and S. Matsuo Endotoxin-Induced Chemokine Expression in Murine Peritoneal Mesothelial Cells: The Role of Toll-Like Receptor 4 J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1289 - 1299. [Abstract] [Full Text] [PDF]

				R. Dechend, J. Gieffers, R. Dietz, A. Joerres, J. Rupp, F. C. Luft, and M. Maass Hydroxymethylglutaryl Coenzyme A Reductase Inhibition Reduces Chlamydia pneumoniae-Induced Cell Interaction and Activation Circulation, July 22, 2003; 108(3): 261 - 265. [Abstract] [Full Text] [PDF]