title: Hyaluronic acid-specific regulation of cytokines by human uterine fibroblasts.
abstract: 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 microg/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.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Terao
mesh_terms: D001769:Blood; D002478:Cells, Cultured; D003470:Culture Media; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000502:physiology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D009844:Oligosaccharides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014599:Uterus / Q000187:drug effects / Q000276:immunology*
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D016207:Cytokines; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D016209:Interleukin-8; D009844:Oligosaccharides; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase