High glucose up-regulates lipopolysaccharide-stimulated inflammatory cytokine production via c-jun N-terminal kinase in the monocytic cell line THP-1

Hirotaka Iwata, Yoshihiko Soga, Michio Meguro, Sayuri Yoshizawa, Yuka Okada, Yoshihiro Iwamoto, Akiko Yamashita, Shogo Takashiba, Fusanori Nishimura

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Diabetic subjects are susceptible to atherosclerosis. It has been postulated that inflammation plays a crucial role in atherogenesis. Since previous studies suggested persistent low-grade infection by Gram-negative bacteria such as Chlamydia spp. and/or periodontal infection is associated with increased atherogenesis among diabetic subjects, we hypothesized that macrophages under hyperglycemia respond to lipopolysaccharide (LPS) challenge in a more exaggerated manner than under normal glucose conditions. Therefore, we examined cytokine productivity and associated signal transduction molecules in LPS-stimulated the monocytic cell line THP-1, under conditions of hyperglycemia. Differentiated THP-1 cells were cultured under normal and high glucose conditions without fetal bovine serum, and were stimulated with Escherichia coli LPS in the presence of LPS binding protein. Following stimulation, activated signal transduction molecules were detected by protein microarray and confirmed thereafter. Results indicated that c-jun N-terminal kinase (JNK) was highly-phosphorylated at high glucose concentrations, and this was confirmed by Western-immunoblotting. Tumor necrosis factor-α and monocyte chemo-attractant protein-1 production were significantly enhanced under these conditions. SP600125, a selective inhibitor of JNK, dose-dependently suppressed the production of these cytokine. Therefore, we suggest that this may be one of the mechanisms by which sub-clinical infection by Gram-negative bacteria promotes atherosclerosis in diabetic subjects.

Original languageEnglish
Pages (from-to)227-234
Number of pages8
JournalJournal of Endotoxin Research
Volume13
Issue number4
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Atherosclerosis
  • Hyperglycemia
  • Infection
  • Inflammatory cytokines
  • JNK
  • Macrophages

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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