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

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 1-7x10(5) 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-kappaB 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.

CD44-Regulated Intracellular Proliferation ofListeria monocytogenes

“…We confirmed previous reports (22,23,26,29,41) indicating that coincubation of cells with LMW HA increased proinflammatory transcripts and demonstrate further that such coincubation diminished listerial growth in macrophages. Eliminating HA via HA'se treatment accelerated listerial proliferation, which is in line with the possibility that macrophage-derived HA acts by binding to hyaloadherins and diminishes listerial growth.…”

Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO2 pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

“…40 Hyalobarrier gel was also proven to be effective in clinical trials, that is, in laparoscopic myomectomy 41,42 and in hysteroscopic surgery. 43,44 The ability of the Hyalobarrier gel in preventing adhesion formation may be explained, in addition to being a barrier, by its inflammatory modulating activity, for example, by induction of interleukin-1, 45,46 interleukin-8, 47 interleukin-12, 48 and tumor necrosis factor alpha 46 production. HA also improved wound healing.…”

Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats

“…It has been shown that GAGs can alter the binding with selectins because the latter bind several glycoproteins [53]. HYA and other GAGs could decrease cytokine gene expression directly [54] or indirectly by binding the CD44 receptor [55]. GAGs might also stimulate or inhibit cell proliferation in different mesothelioma cell lines [56].…”