Human gingival CD14+ fibroblasts primed with gamma interferon increase production of interleukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression

Riyoko Tamai, Tetsuya Sakuta, Kenji Matsushita, Mitsuo Torii, Osamu Takeuchi, Shizuo Akira, Sachiko Akashi, Terje Espevik, Shunji Sugawara, Haruhiko Takada

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36 Citations (Scopus)

Abstract

Gamma interferon (IFN-γ)-primed human gingival fibroblasts (HGF) have been shown to produce higher levels of interleukin-8 (IL-8) upon stimulation with bacterial products and inflammatory cytokines than nonprimed controls. In this study, we examined whether priming of HGF with IFN-γ up-regulates IL-8 production by the cells in response to purified lipopolysaccharide (LPS). The priming effect of IFN-γ was clearly observed in the high-CD14-expressing (CD14high) HGF but not in the low-CD14-expressing (CD14low) HGF. The CD14high HGF were most effectively primed with IFN-γ (1,000 IU/ml) for 72 h. To elucidate the mechanism of the priming effects of IFN-γ for the LPS response by HGF, we examined whether IFN-γ regulated expression of CD14, Toll-like receptor 2 (TLR2), TLR4, MD-2, and MyD88, all of which are molecules suggested to be associated with LPS signaling. In CD14high HGF, IFN-γ markedly up-regulated CD14 and MyD88 but not TLR4 protein and MD-2 mRNA expression, while in CD14low HGF, IFN-γ slightly increased MyD88 and scarcely affected CD14, TLR4 protein, and MD-2 mRNA levels. LPS-induced IL-8 production by IFN-γ-primed CD14high HGF was significantly inhibited by monoclonal antibodies (MAbs) against CD14 and TLR4, but not by an anti-TLR2 MAb. These findings suggested that IFN-γ-primed CD14high HGF to enhance production of IL-8 in response to LPS through augmentation of the CD14-TLR system, where the presence of membrane CD14 was indispensable for the response of HGF to LPS.

Original languageEnglish
Pages (from-to)1272-1278
Number of pages7
JournalInfection and immunity
Volume70
Issue number3
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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