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

被引:273
作者
Biswas, SK
McClure, D
Jimenez, LA
Megson, IL
Rahman, I
机构
[1] Univ Rochester, Med Ctr, Dept Environm Med, Div Lung Biol & Dis, Rochester, NY 14642 USA
[2] Univ Edinburgh, Sch Med, Sch Biomed & Clin Lab Sci, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland
[3] Univ Edinburgh, Sch Med, ELEGI & Colt Res Lab, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland
关键词
D O I
10.1089/ars.2005.7.32
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 muM) 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 (O-2(.-)) 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.
引用
收藏
页码:32 / 41
页数:10
相关论文
共 31 条
  • [1] Aggarwal BB, 2003, ANTICANCER RES, V23, P363
  • [2] CYTOKINE EXPRESSION IN CHRONIC INFLAMMATORY DISEASE
    BRENNAN, FM
    MAINI, RN
    FELDMANN, M
    [J]. BRITISH MEDICAL BULLETIN, 1995, 51 (02) : 368 - 384
  • [3] CURCUMIN, AN ANTITUMOR PROMOTER AND ANTIINFLAMMATORY AGENT, INHIBITS INDUCTION OF NITRIC-OXIDE SYNTHASE IN ACTIVATED MACROPHAGES
    BROUET, I
    OHSHIMA, H
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 206 (02) : 533 - 540
  • [4] Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-κB activation
    Chun, KS
    Keum, YS
    Han, SS
    Song, YS
    Kim, SH
    Surh, YJ
    [J]. CARCINOGENESIS, 2003, 24 (09) : 1515 - 1524
  • [5] Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher
    Das, KC
    Das, CK
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 295 (01) : 62 - 66
  • [6] DEFORGE LE, 1993, J BIOL CHEM, V268, P25568
  • [7] Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression
    Dickinson, DA
    Iles, KE
    Zhang, HQ
    Blank, V
    Forman, HJ
    [J]. FASEB JOURNAL, 2003, 17 (01) : 473 - +
  • [8] Quantification of peroxynitrite, superoxide, and peroxyl radicals by a new spin trap hydroxylamine 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine
    Dikalov, S
    Skatchkov, M
    Bassenge, E
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 230 (01) : 54 - 57
  • [9] DIKSHIT M, 1995, INDIAN J MED RES, V101, P31
  • [10] Adenoviral E1A primes alveolar epithelial cells to PM10-induced transcription of interleukin-8
    Gilmour, PS
    Rahman, I
    Hayashi, S
    Hogg, JC
    Donaldson, K
    MacNee, W
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (03) : L598 - L606