30. Najid A, Simon A, Cook J, Chable-Rabinovitch H, Delage C, et al. (1992) Characterization of ursolic acid as a lipoxygenase and cyclooxygenase inhibitor using macrophages, platelets and differentiated HL60 leukemic cells. FEBS Lett 299: 213–217. 31. Wan F, Lenardo MJ (2010) The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives. Cell Res 20: 24–33. 32. Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2: 725–734. 33. Checker R, Sharma D, Sandur SK, Subrahmanyam G, Krishnan S, et al. (2010) Plumbagin inhibits proliferative and inflammatory responses of T cells independent of ROS generation but by modulating intracellular thiols. J Cell Biochem 110: 1082–1093. 34. Moreau RA, Whitaker BD, Hicks KB (2002) Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health- promoting uses. Prog Lipid Res 41: 457–500. 35. Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117: 1162–1172. 36. Schwartz RH (2003) T cell anergy. Annu Rev Immunol 21: 305–334. 37. Yuan X, Salama AD, Dong V, Schmitt I, Najafian N, et al. (2003) The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo. J Immunol 170: 2949–2955. 38. Curry AJ, Chikwe J, Smith XG, Cai M, Schwarz H, et al. (2004) OX40 (CD134) blockade inhibits the co-stimulatory cascade and promotes heart allograft survival. Transplantation 78: 807–814. 39. Crabtree GR, Clipstone (1994) Signal transmission between the plasma membrane and nucleus of T lymphocytes. Annu Rev Biochem 63: 1045–1083. 40. Hommes DW, Peppelenbosch MP, van Deventer SJ (2003) Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut 52: 144–151. 41. Edmead CE, Patel YI, Wilson A, Boulougouris G, Hall ND, et al. (1996) Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomy- elinase signals. J Immunol 157: 3290–3297. 42. Muraille E, De Smedt T, Thielemans K, Urbain J, Moser M, et al. (1995) Activation of murine T cells by bacterial superantigens requires B7-mediated costimulation. Cell Immunol 162: 315–320. 43. Macian F, Lopez-Rodriguez C, Rao A (2001) Partners in transcription: NFAT and AP-1. Oncogene 20: 2476–2489. 44. Rooney JW, Sun YL, Glimcher LH, Hoey T (1995) Novel NFAT sites that mediate activation of the interleukin-2 promoter in response to T-cell receptor stimulation. Mol Cell Biol 15: 6299–6310. Anti-Inflammatory Effects of Ursolic Acid 45. Rooney JW, Hoey T, Glimcher LH (1995) Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2: 473–483. 46. Sigal NH, Dumont FJ (1992) Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol 10: 519–560. 47. Dumont FJ, Staruch MJ, Koprak SL, Siekierka JJ, Lin CS, et al. (1992) The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin. J Exp Med 176: 751–760. 48. Liu Y, Huang X, Li Y, Li C, Hu X, et al. (2011) Ursolic acid promotes robust tolerance to cardiac allografts in mice. Clin Exp Immunol 164: 282–288. 49. Xu T, Wang X, Zhong B, Nurieva RI, Ding S, et al. (2011) Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein. J Biol Chem 286: 22707–22710. 50. Sharma D, Kumar SS, Raghu R, Khanam S, Sainis KB (2007) Differential modulation of mitogen driven proliferation and homeostasis driven proliferation of T cells by rapamycin, Ly294002 and chlorophyllin. Mol Immunol 44: 2831–2840. 51. Checker R, Chatterjee S, Sharma D, Gupta S, Variyar P, et al. (2008) Immunomodulatory and radioprotective effects of lignans derived from fresh nutmeg mace (Myristica fragrans) in mammalian splenocytes. Int Immuno- pharmacol 8: 661–669. 52. Checker R, Sharma D, Sandur SK, Khanam S, Poduval TB (2009) Anti- inflammatory effects of plumbagin are mediated by inhibition of NF-kappaB activation in lymphocytes. Int Immunopharmacol 9: 949–958. 53. Khan NM, Sandur SK, Checker R, Sharma D, Poduval TB, et al. (2011) Pro- oxidants ameliorate radiation-induced apoptosis through activation of the calcium-ERK1/2-Nrf2 pathway. Free Radic Biol Med 51: 115–128. 54. Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, et al. (2007) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 28: 1765–1773. 55. Kunwar A, Jayakumar S, Bhilwade HN, Bag PP, Bhatt H, et al. (2011) Protective effects of selenocystine against gamma-radiation-induced genotoxicity in Swiss albino mice. Radiat Environ Biophys 50: 271–280. 56. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30: e36. PLoS ONE | www.plosone.org 15 February 2012 | Volume 7 | Issue 2 | e31318