4‐Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts

Taniguchi, Ryousuke; Higuchi, Tsuyoshi; Ozaki, Takashi; Mizunuma, Hideki; Takagaki, Keiichi

doi:10.1111/j.1447-0756.2007.00654.x

Cited by 3 publications

(1 citation statement)

References 17 publications

(38 reference statements)

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“…This dose of 4-MU was demonstrated to be non-toxic to DC as ascertained by staining with 7-AAD and Annexin V (Supplemental Figure 2). This corroborates reports with other cell types that 4-MU at comparable concentrations, is not directly cytotoxic (35–37). Hyaluronidase treatment had the paradoxical effect of increasing DC production of HA (data not shown) as has been shown in other systems (38;39).…”

Section: Resultssupporting

confidence: 92%

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

Bollyky

Evanko

et al. 2010

Cell Mol Immunol

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Hyaluronan (HA) production by dendritic cells (DCs) is known to promote antigen presentation and to augment T-cell activation and proliferation. We hypothesized that pericellular HA can function as intercellular 'glue' directly mediating T cell-DC binding. Using primary human cells, we observed HA-dependent binding between T cells and DCs, which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone (4-MU), an agent which blocks HA synthesis. Furthermore, T cells regulate HA production by DCs via T cell-derived cytokines in a T helper (Th) subset-specific manner, as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production. Similar effects were seen upon the addition of exogenous Th1 cytokines, IL-2, interferon c (IFN-c) and tumor necrosis factor a (TNF-a). The critical factors which determined the extent of DC-T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA, as T-cell clones which were pre-treated with monensin, added to block cytokine secretion, bound equivalently irrespective of their Th subset. These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA, which in turn affects the extent of DC-T cell binding.

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Section: Resultssupporting

confidence: 92%

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

Bollyky

Evanko

et al. 2010

Cell Mol Immunol

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Stimulation of Small Proteoglycan Synthesis by the Hyaluronan Synthesis Inhibitor 4-Methylumbelliferone in Human Skin Fibroblasts

Funahashi

Nakamura

Kakizaki

et al. 2009

Connective Tissue Research

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Human skin fibroblasts cultured with 4-methylumbelliferone (MU), a hyaluronan synthesis inhibitor, produce a hyaluronan-deficient extracellular matrix (See [9]). Our present study investigated the effects of MU on proteoglycan, which is the other main component of the extracellular matrix, and interacts with hyaluronan. Proteoglycans isolated from culture medium in the presence or absence of MU were characterized by gel-filtration chromatography, ion-exchange HPLC, electrophoresis, and immunoblotting. We found that MU had only a negligible effect on the synthesis of large proteoglycan but increased the production of small proteoglycan in comparison with cultures lacking MU. This small proteoglycan was identified by immunoblotting as decorin. The structures of decorin synthesized in the presence and absence of MU were compared by gel-filtration chromatography, and the data indicated that cells incubated with MU produced a larger decorin molecule than cells incubated without MU. Furthermore, the two decorins had galactosaminoglycan chains of different sizes. These results suggest that MU inhibits the synthesis of hyaluronan and accelerates production of the larger decorin in the extracellular matrix.

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Sulfated glycosaminoglycans restore glycocalyx barrier properties of cultured endothelial cells in hyperglycemia

et al. 2008

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4‐Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts

Abstract: MU inhibits the synthesis of hyaluronate in human uterine cervical fibroblasts.

Cited by 3 publications

References 17 publications

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

Stimulation of Small Proteoglycan Synthesis by the Hyaluronan Synthesis Inhibitor 4-Methylumbelliferone in Human Skin Fibroblasts

Sulfated glycosaminoglycans restore glycocalyx barrier properties of cultured endothelial cells in hyperglycemia

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