Hypoxia-inducible factor-1α inhibits interleukin-6 and -8 production in gingival epithelial cells during hypoxia.

BACKGROUND AND OBJECTIVE: Hypoxia has been widely studied in inflammatory diseases as it can modulate the inflammatory response, mainly via the hypoxia-inducible factor (HIF). However, little is known about the effects of hypoxia and the role of HIF in the inflammatory responses to periodontitis. In this study, we focused on the gingival epithelium that is exposed to relatively low levels of oxygen. We investigated whether hypoxic conditions have an impact on inflammatory responses in human gingival epithelial cells (HGECs). MATERIAL AND METHODS: Pimonidazole HCl, which accumulates in hypoxic cells, was administered intraperitoneally to C57BL/6 mice with or without Porphyromonas gingivalis infection. Immunohistochemistry was then performed to detect the hypoxic cells in periodontal tissue. Immortalized HGECs were cultured under hypoxic conditions with or without interleukin (IL)-1ß, and the expression levels of IL-6 and IL-8 were measured by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. HIF-1α expression was detected by western blotting. The DNA-binding activity of HIF-1α was determined by a DNA-binding enzyme-linked immunosorbent assay. The involvement of HIF-1α in the hypoxic response was examined by transfection with HIF-1α siRNA. RESULTS: Immunohistochemistry revealed pimonidazole HCl accumulation in the gingival epithelium of both normal and P. gingivalis-infected mice, with a slightly stronger signal in the P. gingivalis-infected mice than in the normal mice. The IL-1ß-induced IL-6 and IL-8 production by HGECs was suppressed under hypoxic conditions. HIF-1α accumulated during hypoxia, and this accumulation was further enhanced by IL-1ß treatment. The hypoxia-dependent suppression of IL-6 and IL-8 expression was reversed by treating the cells with HIF-1α siRNA. CONCLUSION: Our results suggest that the gingival epithelium is exposed to low oxygen tension in periodontal tissue and that this hypoxic condition modulates the local inflammatory response of gingival epithelial cells in an HIF-1α-dependent manner.

[A case of gastric carcinoma treated effectively with 5'-DFUR].

A 79-year-old male was admitted to our hospital for further examination on gastric carcinoma (1' type) in the cardia. The histology of biopsied tissue was moderately differentiated adenocarcinoma (tub2). The patient refused a gastrectomy and received three cycles of local injection therapy with OK-432 + Beriplast into the tumor. However, the tumor showed no decrease in size. Considering the quality of life, the patient was given out patient treatment with 5'-DFUR (Furtulon, 800 mg/day). Three months later, the patient showed a partial response (PR) on the basis of gastric X-ray and endoscopic findings. No adverse reactions to the drug were seen. The patient has been receiving the same drug since then, and has continued to show PR for 15 months. Biopsied tissues were checked immunohistochemically for expression of thymidine phosphorylase (TdRPase), and changes in tissue TdRPase level were examined by ELISA. The TdRPase level decreased with shrinking of the tumor. These results suggest that the shrinking of tumor following 5'-DFUR therapy is closely related to TdRPase.