title: Expression of urokinase-type plasminogen activator and its receptor in gastric fibroblasts and effects of nonsteroidal antiinflammatory drugs and prostaglandin.
abstract: In acute inflammatory condition, little is known about the expression of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in the gastric fibroblasts. To clarify the role of human gastric fibroblasts in acute inflammatory conditions such as gastric ulcer, the effects of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on the expression of uPA and uPAR, which were suggested to be associated with tissue remodeling, in gastric fibroblasts were investigated. The expression level of uPA mRNA and the amount of uPA antigen increased significantly on treatment with each concentration of IL-1beta (1 and 10 ng/ml) and 10 ng/ml TNF-alpha. On the other hand, the amounts of uPA antigen on cell surfaces were not affected significantly by IL-1beta and TNF-alpha stimulation. The expression level of uPAR mRNA increased in a dose-dependent manner on IL-1beta stimulation. The effect of indomethacin on uPA and uPAR expression in these cells was also examined. When gastric fibroblasts were treated with 50 microM indomethacin, the expression level of uPA mRNA decreased significantly, and the amount of uPA antigen in the culture medium and on cell surfaces decreased significantly with indomethacin in a dose-dependent manner. The increased uPAR mRNA expression caused by IL-1beta was reduced to the basal level by treatment with 50 microM indomethacin. Furthermore, we investigated the role of prostaglandin E2 (PGE2), which is suggested to play major roles in acute inflammation of the stomatch, on uPA and uPAR expression in gastric fibroblasts. The expression level of uPAR mRNA and the amount of uPA antigen on cell surfaces increased in a dose-dependent manner on treatment with PGE2 (10 and 50 ng/ml). These results suggest that uPA and uPAR expression in gastric fibroblasts is involved in the regulating system of PGE2 and that NSAIDs may delay healing of gastric mucosal injury in part through suppressing uPA production via inhibition of endogenous PG production.
authors.affiliation: Fifth Department of Internal Medicine, Tokyo Medical University, Inashiki, Ibaraki, Japan. junnki@dg.mbn.or.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Iwamoto
authors.forename: Kimiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizokami
authors.forename: Toshiya
authors.initials: T
authors.lastname: Otsubo
authors.forename: Syuuhei
authors.initials: S
authors.lastname: Miura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Narasaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Omata
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shimokoube
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuoka
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000941:Antigens / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D017931:DNA Primers; D007375:Interleukin-1; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014409:Tumor Necrosis Factor-alpha; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone; D007213:Indomethacin