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Am J Physiol Cell Physiol 273: C1151-C1159, 1997;
0363-6143/97 $5.00
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Vol. 273, Issue 4, C1151-C1159, October 1997

Hyaluronic acid-specific regulation of cytokines by human uterine fibroblasts

Hiroshi Kobayashi and Toshihiko Terao

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-31, Japan.

The physiological inflammatory response can provide an effective mechanism for delivering the baby at the time of parturition. We characterized the mechanisms by which hyaluronic acid (HA) regulates interleukin-1beta (IL-1beta ), tumor necrosis factor-alpha (TNF-alpha ), and interleukin-8 (IL-8) production in human uterine fibroblasts. A dose-dependent increase in cytokine release was observed over an HA concentration range of 10 µg/ml to 1 mg/ml. The action of HA on the cytokine production is mediated by CD44. Under serum-free conditions, HA-induced cytokine generation was significantly less compared with production in the presence of serum, suggesting involvement of serum proteins. Addition of inter-alpha -trypsin inhibitor (ITI) under serum-free conditions enhanced the HA-induced synthesis of TNF-alpha , which stimulated the temporary release of IL-8. In addition, HA and IL-1beta stimulated the release of hyaluronidase by the fibroblasts. These results indicate that cytokine production in human uterine fibroblasts is regulated in a CD44-HA-ITI-specific fashion. HA may be involved in the regulation of delivery in part through the selective release of cytokines that contribute to uterine cervical ripening.

hyaluronan; interleukin-1; tumor necrosis factor-alpha ; interleukin-8


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