High glucose increases nitric oxide generation in lipopolysaccharide- activated macrophages by enhancing activity of protein kinase C-α/δ and NF-κB

Kuo Feng Hua, Szu Hsuan Wang, Wei Chih Dong, Chai Yi Lin, Chen Lung Ho, Tzu Hua Wu

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21 Citations (Scopus)


Objective: Although several mechanisms by which hyperglycemia modulate inflammation have been proposed, it remains unclear how hyperglycemia regulates inflammation induced by lipopolysaccharide (LPS). Methods: We hypothesized that hyperglycemia might interplay with LPS to modulate the generation of an inflammatory mediator. RAW 264.7 macrophages cultured in medium containing either normal glucose (5.5-mM) or high glucose (HG) (15- and 25-mM) were treated with LPS. The nitric oxide (NO) generation, inducible NO synthase (iNOS) expression and cytokine release were then quantified by Griess reaction, western blot, and enzymelinked immunosorbent assay (ELISA) respectively. The effect of HG on the activation of kinase and Nuclear Factor-Kappa B (NF-κB) were measured by western blot and NF-κB reporter assay respectively. Results: Without LPS stimulation, HG alone did not induce NO generation and cytokine secretion; but LPSinduced NO generation, iNOS expression, and interleukin-1beta (IL-1β) secretion were higher in HG-cultured cells than in normal glucose-cultured cells. In contrast, LPSinduced interleukin-6 (IL-6) and tumor necrosis factoralpha (TNF-α) secretion were lower in HG-cultured cells than in normal glucose-cultured cells. Furthermore, HG increased iNOS expression and NO generation by enhancing phosphorylation levels of protein kinase C-alpha (PKC-α), protein kinase C-delta (PKC-δ), and p38 phosphorylation and NF-κB transcriptional activity. Conclusions: This study revealed a possible role of PKC-α and PKC-δ potentially involved in diabetes-promoted inflammation.

Original languageEnglish
Pages (from-to)1107-1116
Number of pages10
JournalInflammation Research
Issue number10
Publication statusPublished - Oct 2012



  • Hyperglycemia
  • Inflammation
  • LPS
  • PKC

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

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