Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity.
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.
Biswas
Saibal K
SK
Centre for Cardiovascular Sciences, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, Medical School, Edinburgh, UK.
McClure
Danny
D
Jimenez
Luis A
LA
Megson
Ian L
IL
Rahman
Irfan
I
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D016209:Interleukin-8; D016328:NF-kappa B; D010880:Piperidines; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C103674:1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidine; D006861:Hydrogen Peroxide; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003474:Curcumin; D010100:Oxygen