Gold nanoparticles attenuate LPS-induced NO production through the inhibition of NF-kappa B and IFN-beta/STAT1 pathways in RAW264.7 cells

Macrophage-derived nitric oxide (NO) plays an important role in protection against microbial infection in immune responses. Overproduction of NO by inducible nitric synthase (iNOS) is known to be closely correlated with the pathology of a variety of diseases and inflammations. In this study, we investigated the inhibitory effect of polyethylene glycol coated gold nanoparticles (GNP) on NO production and its molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It was found that GNP inhibited LPS-induced NO production and iNOS expression in RAW264.7 cells. Furthermore, GNP suppressed LPS-induced activation of NF-kappa B through the inhibition of Akt activity. GNP also inhibited LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) via down-regulation of interferon-beta (IFN-beta) expression. Our results suggest that GNP inhibits NO production and iNOS expression through blocking the activation of NF-kappa B and STAT1 in LPS-stimulated RAW264.7 cells. (C) 2010 Elsevier Inc. All rights reserved.Yen HJ, 2009, SMALL, V5, P1553, DOI 10.1002/smll.200900126Niethammer P, 2009, NATURE, V459, P996, DOI 10.1038/nature08119OUTI S, 2008, INT IMMUNOPHARMACOL, V8, P100Jung CH, 2007, J ETHNOPHARMACOL, V113, P183, DOI 10.1016/j.jep.2007.05.023Hsu SH, 2006, J BIOMED MATER RES A, V79A, P759, DOI 10.1002/bm.a.30879Lim YT, 2006, ADV FUNCT MATER, V16, P1015, DOI 10.1002/adfm.200500860Akira S, 2006, CELL, V124, P783, DOI 10.1016/j.cell.2006.02.015Shukla R, 2005, LANGMUIR, V21, P10644, DOI 10.1021/la0513712Fortina P, 2005, TRENDS BIOTECHNOL, V23, P168, DOI 10.1016/j.tibtech.2005.02.007Deonarain R, 2004, CIRCULATION, V110, P3540, DOI 10.1161/01.CIR.0000136824.73458.20Akira S, 2004, NAT REV IMMUNOL, V4, P499, DOI 10.1038/nri1391Hattori Y, 2003, EUR J PHARMACOL, V481, P153, DOI 10.1016/j.ejphar.2003.09.034Duffield JS, 2003, CLIN SCI, V104, P27MARINA K, 2003, NAT IMMUNOL, V4, P471Swindle EJ, 2002, J IMMUNOL, V169, P5866Chang H, 2002, CAN J ANAESTH, V49, P477Toshchakov V, 2002, NAT IMMUNOL, V3, P392, DOI 10.1038/ni774Kawai T, 2001, J IMMUNOL, V167, P5887Chung HT, 2001, BIOCHEM BIOPH RES CO, V282, P1075Ohmori Y, 2001, J LEUKOCYTE BIOL, V69, P598Chan ED, 2001, AM J PHYSIOL-CELL PH, V280, pC441Guha M, 2001, CELL SIGNAL, V13, P85Detmers PA, 2000, J IMMUNOL, V165, P3430Jeon YJ, 2000, J PHARMACOL EXP THER, V294, P548Pan MH, 2000, BIOCHEM PHARMACOL, V59, P357Guan ZH, 1999, J BIOL CHEM, V274, P36200Karin M, 1999, J BIOL CHEM, V274, P27339Hobbs AJ, 1999, ANNU REV PHARMACOL, V39, P191Gao JJ, 1998, J IMMUNOL, V161, P4803Ghosh S, 1998, ANNU REV IMMUNOL, V16, P225MacMicking J, 1997, ANNU REV IMMUNOL, V15, P323Baeuerle PA, 1997, ADV IMMUNOL, V65, P111LIU RH, 1995, MUTAT RES-REV GENET, V339, P73MULLER U, 1994, SCIENCE, V264, P1918XIE QW, 1994, J BIOL CHEM, V269, P4705MARIETTA MA, 1993, J BIOL CHEM, V268, P12231NATHAN C, 1992, FASEB J, V6, P3051XIE QW, 1992, SCIENCE, V256, P228PETROS A, 1991, LANCET, V338, P1557MONCADA S, 1991, PHARMACOL REV, V43, P109ADAMS DO, 1984, ANNU REV IMMUNOL, V2, P283