Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity

Antioxid Redox Signal. Jan-Feb 2005;7(1-2):32-41. doi: 10.1089/ars.2005.7.32.

Abstract

Oxidants and tumor necrosis factor-alpha (TNF-alpha) activate transcription factors such as nuclear factor-kappaB (NF-kappaB), which is involved in the transcription of proinflammatory mediators, including interleukin-8 (IL-8). Curcumin (diferuloylmethane) is a naturally occurring flavonoid present in the spice turmeric, which has a long traditional use as a chemotherapeutic agent for many diseases. We hypothesize that curcumin may possess both antioxidant and antiinflammatory properties by increasing the glutathione levels and inhibiting oxidant- and cytokine-induced NF-kappaB activation and IL-8 release from cultured alveolar epithelial cells (A549). Treatment of A549 cells with hydrogen peroxide (H2O2; 100 microM) and TNF-alpha (10 ng/ml) significantly increased NF-kappaB and activator protein-1 (AP-1) activation, as well as IL-8 release. Curcumin inhibited both H2O2- and TNF-alpha-mediated activation of NF-kappaB and AP-1, and IL-8 release. Furthermore, an increased level of GSH and glutamylcysteine ligase catalytic subunit mRNA expression was observed in curcumin-treated cells as compared with untreated cells. Curcumin interacted directly with superoxide anion (O2*-) and hydroxyl radical (*OH) as shown by electron paramagnetic resonance, quenching the interaction of the radicals with the spin trap, Tempone-H. This suggests that curcumin has multiple properties: as an oxygen radical scavenger, antioxidant through modulation of glutathione levels, and antiinflammatory agent through inhibition of IL-8 release in lung cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Curcumin / pharmacology*
  • Electron Spin Resonance Spectroscopy
  • Enzyme Inhibitors / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Free Radical Scavengers / pharmacology*
  • Free Radicals
  • Glutamate-Cysteine Ligase / metabolism
  • Glutathione / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Interleukin-8 / metabolism*
  • Models, Chemical
  • NF-kappa B / metabolism*
  • Oxygen / metabolism
  • Piperidines / pharmacology
  • Pulmonary Alveoli / cytology*
  • Pulmonary Alveoli / drug effects
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Free Radicals
  • Interleukin-8
  • NF-kappa B
  • Piperidines
  • RNA, Messenger
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • 1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidine
  • Hydrogen Peroxide
  • Glutamate-Cysteine Ligase
  • Glutathione
  • Curcumin
  • Oxygen