Modulation of Hyaluronan Fragmentation by Interleukin-1 Beta in Synovial Membrane Cells

Abstract

Hyaluronan (HA) plays a crucial role in the lubricating and buffering properties of synovial fluid. The purpose of this study was to examine the effects of interleukin (IL)-1beta on HA degradation in cultured synovial membrane cells. The rabbit synovial membrane cell line HIG-82 was cultured with and without IL-1beta. The amounts of HA of varying molecular weights in the medium were analyzed using high-performance liquid chromatography, the mRNA levels of HA synthase (HAS) and hyaluronidase (HYAL) were analyzed by means of real-time PCR, and HYAL activity was analyzed by HA zymography. The amounts of HA with a molecular weight lower than 300 kDa, and between 300 and 1900 kDa, in the culture medium of HIG-82 cells were significantly higher in the presence of IL-1beta. However, the amount of HA with a molecular weight greater than 1900 kDa was significantly lower in the presence of IL-1beta. Both HAS2 and HAS3 mRNA levels were upregulated by treatment with IL-1beta. So, too, were the levels of HYAL1 and HYAL2 mRNA, which resulted in enhanced HYAL activity. However, HYAL activity was inhibited by transfection of HYAL2-siRNA. Our results suggest that IL-1beta is a crucial factor in the fragmentation of HA in inflammatory joints.

Effects of Low-Intensity Pulsed Ultrasound on the Expression and Activity of Hyaluronan Synthase and Hyaluronidase in IL-1β-Stimulated Synovial Cells

“…These results of HAS2 and HAS3 are the same as our previous results. 40 In this study, LIPUS enhanced the HAS2 expression markedly and down-regulated the HYAL2 expression in the IL-1b-stimulated synovial membrane cells, while the expression of HAS3 was slightly elevated. Therefore, these results suggest that LIPUS enhanced synthesis of high-molecular weight HA, indicating anti-inflammatory response.…”

“…39 HYAL1 and HYAL2 were detected in rabbit synovial membrane cells. 40 HYAL1 was reported to have a different expression from HYAL2, and to digest small fragments of HA produced by HYAL2 activity, 6 namely HYAL2 cleaves high-molecular weight HA to a limit product of approximately 20 kDa, whereas HYAL1 appears to be lysosomal enzyme, cleaving HA to predominantly tetra-saccharides. However, the detailed function of HYAL1 in HA degradation has not been fully elucidated.…”

“…In addition, the previous study revealed that the degradation of HA induced by IL-1b was at least partially due to increased HYAL2 activity, whereas the expression of HYAL1 was down-regulated by IL-1b treatment. 40 Therefore, in this study, the expression levels of HAS2, HAS3, and HYAL2 mRNAs were analyzed to evaluate the HA metabolism in cultured synovial membrane cells.…”

A link between smooth muscle cell death and extracellular matrix degradation during vascular atrophy

“…FasL also induces MCP-1 in SMCs in vitro (our results and 16), and increased blood flow increases MCP-1 in the PTFE graft model after 4 days (online table 8C in Hsieh et al9), but not after 1 day (online Tables I and II). In addition, induction of MCP-1 is partially mediated by IL-1α (Schaub et al 2000), which also induces ADAMTS4 and hyaluronidase 270–71. These data suggest that a Fas/IL-1α pathway may be operative in vivo during atrophy and account for the up-regulation of some of the atrophy-associated genes.…”

Hyaluronan in part mediates IL-1beta-induced inflammation in mouse chondrocytes by up-regulating CD44 receptors

“…The inflammatory cytokine IL-1β plays a crucial role in the induction of degradative metabolic events in articular cartilage during arthritis (Ferraccioli et al, 2010;Tanimoto et al, 2010). This degradative action leads to the production of a substantial number of small HA fragments that contribute greatly to the amplification and extension of the inflammatory process (Jiang et al, 2011).…”