Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation

Authors:
  • TMTakashi Morisaki
    Takashi Morisaki
  • KIKenji Izuhara
    Kenji Izuhara
  • AUAkihiko Uchiyama
    Akihiko Uchiyama
  • YMYasuo Matsunari
    Yasuo Matsunari
  • MKMitsuo Katano
    Mitsuo Katano
  • MTMasao Tanaka
    Masao Tanaka

Abstract
Both nonneoplastic colon epithelium and colon carcinoma cells in situ are continuously exposed to lipopolysaccharide (LPS). Few reports have addressed possible direct effects of LPS in promotion of colon carcinoma and underlying mechanisms. We found evidence that LPS directly stimulated growth of the human colon carcinoma cell line CE-1 through an increase in the production of prostaglandin E2 (PGE2) as a result of cyclo-oxygenase-2 (COX-2) expression. LPS induced significant increases in PGE2 production in CE-1 cells, which were found to express a high-affinity LPS receptor, CD14. Positive correlations were found between PGE2 production and activation of nuclear factor (NF)-kappa B as well as expression of both COX-2 mRNA and protein in LPS-stimulated CE-1 cells. When CE-1 cells were exposed to exogenous PGE2, DNA synthesis increased. These results indicate that LPS may stimulate DNA synthesis in certain colon carcinoma cells as a result of PGE2 production involving increased COX-2 expression that might result in turn from activation of NF-kappa B by LPS. Further investigation of the pathways mediating LPS-induced stimulation of colon carcinoma cells may provide insights into LPS effects in in vivo tumor biology.

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