High glucose induces IL-1β expression in human monocytes: Mechanistic insights

Mohan R. Dasu, Sridevi Devaraj, Ishwarlal Jialal

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Previously, IL-1β secretion from Type 2 diabetic patients has been shown to be increased compared with controls. In this study, we aimed to delineate the mechanism of IL-1β induction under high-glucose (HG) conditions in human monocytes. THP-1 cells cultured in normal glucose were treated with increasing concentrations of D-glucose (10-25 mM) for 6-72 h. IL-1β and IL-1 receptor antagonist levels were measured by ELISA and Western blots, whereas mRNA was quantitated by RTPCR. Specific inhibitors and small interfering RNAs of PKC, p38, ERK1/2, NF-κB, and NADPH oxidase were used to determine the mediators in parallel experiments under HG conditions. IL-1β-secreted protein, cellular protein, and mRNA increase under HG conditions is time and dose dependent, with maximum increase at 15 mM (48 h; P < 0.05). IL-1 receptor antagonist release was time and dose dependent, similar to IL-1β expression pattern; however, the molar ratio of IL-1β to IL-1RA was increased. Data from inhibitor and small interfering RNA experiments indicate that IL-1β release under HG is mediated by PKC-α, via phosphorylation of p38 MAPK, and ERK1/2 leading to NF-κB activation, resulting in increased mRNA and protein for IL-1β. At the same time, it appears that NADPH oxidase via p47phox activates NF-κB, resulting in increased IL-1β secretion. Data suggest that, under HG conditions, monocytes release significantly higher amounts of IL-1β through multiple mechanisms, further compounding the disease progression. Targeting signaling pathways mediating IL-1β release could result in the amelioration of inflammation and possibly diabetic vasculopathies.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume293
Issue number1
DOIs
StatePublished - Jul 2007

Fingerprint

Interleukin-1
Monocytes
Glucose
Interleukin-1 Receptors
NADPH Oxidase
Messenger RNA
Small Interfering RNA
Phosphorylation
Proteins
p38 Mitogen-Activated Protein Kinases
Disease Progression
Cultured Cells
Western Blotting
Experiments
Chemical activation
Enzyme-Linked Immunosorbent Assay
Inflammation

Keywords

  • Diabetes
  • Interleukin-1β
  • p38 phosphorylation
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

High glucose induces IL-1β expression in human monocytes : Mechanistic insights. / Dasu, Mohan R.; Devaraj, Sridevi; Jialal, Ishwarlal.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 293, No. 1, 07.2007.

Research output: Contribution to journalArticle

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