Cell and Tissue Research

, Volume 305, Issue 1, pp 79–86

Hyaluronan fragments induce the synthesis of MCP-1 and IL-8 in cultured human peritoneal mesothelial cells

  • Bettina Haslinger
  • Sonja Mandl-Weber
  • Alois Sellmayer
  • Thomas Sitter
Regular Article

DOI: 10.1007/s004410100409

Cite this article as:
Haslinger, B., Mandl-Weber, S., Sellmayer, A. et al. Cell Tissue Res (2001) 305: 79. doi:10.1007/s004410100409

Abstract.

Human peritoneal mesothelial cells (HMC) play an important role in inflammatory processes by their ability to produce various cytokines and chemokines, such as monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8). In this study we investigated the effect of experimentally generated hyaluronan (HA) fragments, degradation products of the extracellular matrix component hyaluronan, which accumulate at inflammatory sites, on the expression of MCP-1 and IL-8 in cultured HMC. MCP-1 and IL-8 mRNA expression was determined by RNase protection assays, and protein levels in the supernatants were measured by enzyme-linked immunosorbent assays. HA fragments with a molecular mass of approximately 1–7×105 daltons upregulate MCP-1 and IL-8 synthesis in HMC dose and time dependently. The effect of HA fragments could be blocked by Ro31-8220, a specific protein kinase C inhibitor, and by PD98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Upregulation of chemokine synthesis was preceded by an increase in NF-κB and AP-1 DNA-binding activity, suggesting that these transcription factors are activated to increase MCP-1 and IL-8 expression by HA fragments. These data demonstrate that HA fragments markedly enhance the mRNA expression and protein synthesis of MCP-1 and IL-8 in HMC. In concert with previous findings, our observations indicate that enhanced levels of HA, which are present in the peritoneal cavity of peritoneal dialysis patients, may account for a locally increased chemokine production.

Mesothelial cells Hyaluronan Chemokines Peritoneal dialysis MAPK cascade Human 

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Bettina Haslinger
    • 1
  • Sonja Mandl-Weber
    • 1
  • Alois Sellmayer
    • 1
  • Thomas Sitter
    • 1
  1. 1.Medizinische Klinik Innenstadt, Klinikum der Ludwig-Maximilians Universität, Ziemssenstr. 1, 80336 Munich, GermanyGermany