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Inhibition of TNFα-induced iNOS expression in HSV-tk transduced 9L glioblastoma cell lines by Marasmius oreades substances through NF-κB- and MAPK-dependent mechanisms

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Abstract

Nitric oxide (NO) is a gaseous, radical molecule that plays a role in various physiological processes. Previously, we reported that transduction of murine colon cancer cells (MC38) with herpes simplex virus thymidine kinase (HSV-tk) gene resulted in a significant over-expression of cyclooxygenase-2 (COX-2) and activation of NF-kB pathway. In this study we show that TNFα, but not LPS, was significantly able to stimulate the production of NO in HSV-tk transduced 9L glioblastoma cell lines, mediated by the up-regulation of iNOS transcript and iNOS protein. The TNFα-induced up-regulation of iNOS expression was mediated by MAPK and NF-κB signaling pathways as revealed by using selective pharmaceutical inhibitors. A culture liquid extract of the edible and medicinal mushroom Marasmius oreades that was previously shown to inhibit iNOS expression in MCF-7 was utilized to prepare fractions and evaluate their ability to affect TNFα-induced iNOS expression in HSV tk transduced 9L cell lines. While most of the tested fractions were shown to inhibit TNFα-induced iNOS expression, they targeted different signaling pathways in a selective fashion. Here, we report that fraction SiSiF1 interfered with IKBα phosphorylation and consequently interfered with NF-κB activation pathway. SiSiF1 showed minimal interference with the phosphorylation of p38 and JNK proteins. In contrast, fraction SiSiF3 selectively inhibited the phosphorylation of p38 and fractions SiSiF4 and SiSiF5 selectively inhibited the phosphorylation of JNK with no observed effect against IKBα and p38 phosphorylation. Our data illustrate the complexity of iNOS regulation in HSV tk transduced 9L cell lines and also the richness of natural products with bioactive substances that may act synergistically through different signaling pathways to affect iNOS gene expression.

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Abbreviations

IκBα:

Inhibitory proteins kappa B

IKK:

IkB kinase complex

INOS:

Inducible nitric oxide synthase

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

NF-κB:

Nuclear factor kappa B

TNF-α:

Tumor necrosis factor α

References

  1. Rao KM (2000) Molecular mechanisms regulating iNOS expression in various cell types. J Toxicol Environ Health B Crit Rev 3:27–58. doi:10.1080/109374000281131

    Article  CAS  PubMed  Google Scholar 

  2. Chu SC, Marks-Konczalik J, Wu HP, Banks TC, Moss J (1998) Analysis of the cytokine-stimulated human inducible nitric oxide synthase (iNOS) gene: characterization of differences between human and mouse iNOS promoters. Biochem Biophys Res Commun 248:871–878. doi:10.1006/bbrc.1998.9062

    Article  CAS  PubMed  Google Scholar 

  3. Ganster RW, Taylor BS, Shao L, Geller DA (2001) Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-kappa B. Proc Natl Acad Sci USA 98:8638–8643. doi:10.1073/pnas.151239498

    Article  CAS  PubMed  Google Scholar 

  4. Pan D, Bera AK, Das S, Bandyopadhyay S, Rana T, Bandyopadhyay S, Das SK, Bhattacharya D (2009) Use of zinc chloride as alternative stimulant for in vitro study of nitric oxide production pathway in avian splenocyte culture. Mol Biol Rep. doi:10.1007/s11033-009-9708-y

  5. Chartrain NA, Geller DA, Koty PP, Sitrin NF, Nussler AK, Hoffman EP, Billiar TR, Hutchinson NI, Mudgett JS (1994) Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene. J Biol Chem 269:6765–6772

    CAS  PubMed  Google Scholar 

  6. Nishiya T, Uehara T, Nomura Y (1995) Herbimycin A suppresses NF-kappa B activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells. FEBS Lett 371:333–336. doi:10.1016/0014-5793(95)00933-Z

    Article  CAS  PubMed  Google Scholar 

  7. Zongze Z, Jia Z, Chang C, Kai C, Yanlin W (2009) Protective effects of remifentanil on septic mice. Mol Biol Rep. doi:10.1007/s11033-009-9828-4

  8. Song XM, Wang YL, Li JG, Wang CY, Zhou Q, Zhang ZZ, Liang H (2009) Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Mol Biol Rep 36:2345–2351. doi:10.1007/s11033-009-9456-z

    Article  CAS  PubMed  Google Scholar 

  9. Ying B, Yang T, Song X, Hu X, Fan H, Lu X, Chen L, Cheng D, Wang T, Liu D, Xu D, Wei Y, Wen F (2009) Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways. Mol Biol Rep 36:1825–1832. doi:10.1007/s11033-008-9386-1

    Article  CAS  PubMed  Google Scholar 

  10. Petrova RD, Mahajna J, Reznick AZ, Wasser SP, Denchev CM, Nevo E (2007) Fungal substances as modulators of NF-kappaB activation pathway. Mol Biol Rep 34:145–154. doi:10.1007/s11033-006-9027-5

    Article  CAS  PubMed  Google Scholar 

  11. Lull C, Wichers HJ, Savelkoul HF (2005) Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm 2005:63–80. doi:10.1155/MI.2005.63

    Article  PubMed  Google Scholar 

  12. Park YM, Kim IT, Park HJ, Choi JW, Park KY, Lee JD, Nam BH, Kim DG, Lee JY, Lee KT (2004) Anti-inflammatory and anti-nociceptive effects of the methanol extract of Fomes fomentarius. Biol Pharm Bull 27:1588–1593

    Article  CAS  PubMed  Google Scholar 

  13. Rether J, Erkel G, Anke T, Sterner O (2004) Inhibition of inducible TNF-alpha expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale. Biol Chem 385:829–834. doi:10.1515/BC.2004.108

    Article  CAS  PubMed  Google Scholar 

  14. Mattila P, Konko K, Eurola M, Pihlava JM, Astola J, Vahteristo L, Hietaniemi V, Kumpulainen J, Valtonen M, Piironen V (2001) Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J Agric Food Chem 49:2343–2348

    Article  CAS  PubMed  Google Scholar 

  15. Nakamura T, Akiyama Y, Matsugo S, Uzuka Y, Shibata K, Kawagishi H (2003) Purification of caffeic acid as an antioxidant from submerged culture mycelia of Phellinus linteus (Berk. et Curt.) Teng (Aphyllophoromycetideae). Int J Med Mushroom 5:163–167. doi:10.1615/InterJMedicMush.v5.i2.50

    Article  CAS  Google Scholar 

  16. Kim HG, Shrestha B, Lim SY, Yoon DH, Chang WC, Shin DJ, Han SK, Park SM, Park JH, Park HI, Sung JM, Jang Y, Chung N, Hwang KC, Kim TW (2006) Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol 545:192–199. doi:10.1016/j.ejphar.2006.06.047

    Article  CAS  PubMed  Google Scholar 

  17. Lorenzen K, Anke T (1998) Basidiomycetes as a source for new bioactive natural products. Curr Org Chem 2:329–364

    CAS  Google Scholar 

  18. Anke T, Kupka J, Schramm G, Steglich W (1980) Antibiotics from basidiomycetes. X. Scorodonin, a new antibacterial and antifungal metabolite from Marasmius scorodonius (Fr.) Fr. J Antibiot (Tokyo) 33:463–467

    CAS  Google Scholar 

  19. Davies DG, Hodge P (2005) Biosynthesis of the allene (−)-marasin in Marasmius ramealis. Org Biomol Chem 3:1690–1693. doi:10.1039/b502785n

    Article  CAS  PubMed  Google Scholar 

  20. Tobe Y, Dai Y, Tohru T, Masashi I, Junichi S, Kiyomi K, Kazuya K, Yoshinobu O (1990) Synthesis of (. +−.)-marasmic acid via 1-oxaspirohexane rearrangement. J Am Chem Soc 112:775–779. doi:10.1021/ja00158a042

    Article  CAS  Google Scholar 

  21. Konson A, Ben-Kasus T, Mahajna JA, Danon A, Rimon G, Agbaria R (2004) Herpes simplex virus thymidine kinase gene transduction enhances tumor growth rate and cyclooxygenase-2 expression in murine colon cancer cells. Cancer Gene Ther 11:830–840. doi:10.1038/sj.cgt.7700768

    Article  CAS  PubMed  Google Scholar 

  22. Konson A, Mahajna JA, Danon A, Rimon G, Agbaria R (2006) The involvement of nuclear factor-kappa B in cyclooxygenase-2 overexpression in murine colon cancer cells transduced with herpes simplex virus thymidine kinase gene. Cancer Gene Ther 13:1093–1104. doi:10.1038/sj.cgt.7700983

    Article  CAS  PubMed  Google Scholar 

  23. Garvey EP, Oplinger JA, Furfine ES, Kiff RJ, Laszlo F, Whittle BJ, Knowles RG (1997) 1400 W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo. J Biol Chem 272:4959–4963. doi:10.1074/jbc.272.8.4959

    Article  CAS  PubMed  Google Scholar 

  24. Moore PK, Babbedge RC, Wallace P, Gaffen ZA, Hart SL (1993) 7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure. Br J Pharmacol 108:296–297

    CAS  PubMed  Google Scholar 

  25. Narayanan K, Griffith OW (1994) Synthesis of l-thiocitrulline, l-homothiocitrulline, and S-methyl-l-thiocitrulline: a new class of potent nitric oxide synthase inhibitors. J Med Chem 37:885–887. doi:10.1021/jm00033a004

    Article  CAS  PubMed  Google Scholar 

  26. Sweeney WE, Chen Y, Nakanishi K, Frost P, Avner ED (2000) Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney Int 57:33–40. doi:10.1046/j.1523-1755.2000.00829.x

    Article  CAS  PubMed  Google Scholar 

  27. Jaleel M, Shenoy AR, Visweswariah SS (2004) Tyrphostins are inhibitors of guanylyl and adenylyl cyclases. Biochemistry 43:8247–8255. doi:10.1021/bi036234n

    Article  CAS  PubMed  Google Scholar 

  28. Kamon J, Yamauchi T, Muto S, Takekawa S, Ito Y, Hada Y, Ogawa W, Itai A, Kasuga M, Tobe K, Kadowaki T (2004) A novel IKKbeta inhibitor stimulates adiponectin levels and ameliorates obesity-linked insulin resistance. Biochem Biophys Res Commun 323:242–248. doi:10.1016/j.bbrc.2004.08.083

    Article  CAS  PubMed  Google Scholar 

  29. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA 98:13681–13686

    Article  CAS  PubMed  Google Scholar 

  30. Shin M, Yan C, Boyd D (2002) An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding and PMA-inducible 92-kDa type IV collagenase expression. Biochim Biophys Acta 1589:311–316. doi:10.1016/S0167-4889(02)00195-7

    Article  CAS  PubMed  Google Scholar 

  31. Ajizian SJ, English BK, Meals EA (1999) Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis 179:939–944. doi:10.1086/314659

    Article  CAS  PubMed  Google Scholar 

  32. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187. doi:10.1038/35012076

    Article  CAS  PubMed  Google Scholar 

  33. Lacoste J, Cohen L, Hiscott J (1991) NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I. Virology 184:553–562

    Article  CAS  PubMed  Google Scholar 

  34. Means TK, Pavlovich RP, Roca D, Vermeulen MW, Fenton MJ (2000) Activation of TNF-alpha transcription utilizes distinct MAP kinase pathways in different macrophage populations. J Leukoc Biol 67:885–893

    CAS  PubMed  Google Scholar 

  35. Demarchi F, d’Adda di Fagagn F, Falaschi A, Giacca M (1996) Activation of transcription factor NF-kappaB by the Tat protein of human immunodeficiency virus type 1. J Virol 70:4427–4437

    CAS  PubMed  Google Scholar 

  36. Hirai H, Suzuki T, Fujisawa J, Inoue J, Yoshida M (1994) Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation. Proc Natl Acad Sci USA 91:3584–3588

    Article  CAS  PubMed  Google Scholar 

  37. Su F, Schneider RJ (1996) Hepatitis B virus HBx protein activates transcription factor NF-kappaB by acting on multiple cytoplasmic inhibitors of rel-related proteins. J Virol 70:4558–4566

    CAS  PubMed  Google Scholar 

  38. Sylla BS, Hung SC, Davidson DM, Hatzivassiliou E, Malinin NL, Wallach D, Gilmore TD, Kieff E, Mosialos G (1998) Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-kappaB through a pathway that includes the NF-kappaB-inducing kinase and the IkappaB kinases IKKalpha and IKKbeta. Proc Natl Acad Sci USA 95:10106–10111

    Article  CAS  PubMed  Google Scholar 

  39. Benencia F, Courreges MC (1999) Nitric oxide and macrophage antiviral extrinsic activity. Immunology 98:363–370. doi:10.1046/j.1365-2567.1999.00864.x

    Article  CAS  PubMed  Google Scholar 

  40. Paludan SR, Ellermann-Eriksen S, Mogensen SC (1998) NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages. J Gen Virol 79(Pt 11):2785–2793

    CAS  PubMed  Google Scholar 

  41. Patel A, Hanson J, McLean TI, Olgiate J, Hilton M, Miller WE, Bachenheimer SL (1998) Herpes simplex type 1 induction of persistent NF-kappa B nuclear translocation increases the efficiency of virus replication. Virology 247:212–222

    Article  CAS  PubMed  Google Scholar 

  42. Feinstein DL, Galea E, Roberts S, Berquist H, Wang H, Reis DJ (1994) Induction of nitric oxide synthase in rat C6 glioma cells. J Neurochem 62:315–321. doi:10.1111/j.1471-4159.1994.tb08408.x

    Article  CAS  PubMed  Google Scholar 

  43. Bhat NR, Shen Q, Fan F (2003) TAK1-mediated induction of nitric oxide synthase gene expression in glial cells. J Neurochem 87:238–247. doi:10.1046/j.1471-4159.2003.01998.x

    Article  CAS  PubMed  Google Scholar 

  44. Hua LL, Zhao ML, Cosenza M, Kim MO, Huang H, Tanowitz HB, Brosnan CF, Lee SC (2002) Role of mitogen-activated protein kinases in inducible nitric oxide synthase and TNFalpha expression in human fetal astrocytes. J Neuroimmunol 126:180–189. doi:10.1016/S0165-5728(02)00107-8

    Article  CAS  PubMed  Google Scholar 

  45. Kim YJ, Hwang SY, Oh ES, Oh S, Han IO (2006) IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. J Neurosci Res 84:1037–1046. doi:10.1002/jnr.21011

    Article  CAS  PubMed  Google Scholar 

  46. Pawate S, Bhat NR (2006) C-Jun N-terminal kinase (JNK) regulation of iNOS expression in glial cells: predominant role of JNK1 isoform. Antioxid Redox Signal 8:903–909. doi:10.1089/ars.2006.8.903

    Article  CAS  PubMed  Google Scholar 

  47. Jiang B, Brecher P, Cohen RA (2001) Persistent activation of nuclear factor-{kappa}B by interleukin-1{beta} and subsequent inducible NO synthase expression requires extracellular signal-regulated kinase. Arterioscler Thromb Vasc Biol 21:1915–1920. doi:10.1161/hq1201.099424

    Article  CAS  PubMed  Google Scholar 

  48. Schindler C, Darnell JE Jr (1995) Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 64:621–651. doi:10.1146/annurev.bi.64.070195.003201

    Article  CAS  PubMed  Google Scholar 

  49. Doi M, Shichiri M, Katsuyama K, Ishimaru S, Hirata Y (2002) Cytokine-activated Jak-2 is involved in inducible nitric oxide synthase expression independent from NF-kappaB activation in vascular smooth muscle cells. Atherosclerosis 160:123–132. doi:10.1016/S0021-9150(01)00578-0

    Article  CAS  PubMed  Google Scholar 

  50. Nakashima O, Terada Y, Inoshita S, Kuwahara M, Sasaki S, Marumo F (1999) Inducible nitric oxide synthase can be induced in the absence of active nuclear factor-kappaB in rat mesangial cells: involvement of the Janus kinase 2 signaling pathway. J Am Soc Nephrol 10:721–729

    CAS  PubMed  Google Scholar 

  51. Lindequist U, Niedermeyer TH, Julich WD (2005) The pharmacological potential of mushrooms. Evid Based Complement Altern Med 2:285–299. doi:10.1093/ecam/neh107

    Article  Google Scholar 

  52. Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65–96

    CAS  PubMed  Google Scholar 

  53. Yassin M, Mahajna J, Wasser SP (2003) Submerged cultured mycelium extracts of higher basidiomycetes mushroom selectively inhibit proliferation and induce differentiation of K562 human chronic myelogenous leukemia cells. Int J Med Mushroom 5:259–274. doi:10.1615/InterJMedicMush.v5.i3.40

    Google Scholar 

  54. Zaidman BZ, Wasser SP, Nevo E, Mahajna J (2007) Androgen receptor-dependent and -independent mechanisms mediate Ganoderma lucidum activities in LNCaP prostate cancer cells. Int J Oncol 31:959–967

    CAS  PubMed  Google Scholar 

  55. Zaidman BZ, Wasser SP, Nevo E, Mahajna J (2008) Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. Mol Biol Rep 35:107–117. doi:10.1007/s11033-007-9059-5

    Article  CAS  PubMed  Google Scholar 

  56. Zaidman BZ, Yassin M, Mahajna J, Wasser SP (2005) Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol 67:453–468. doi:10.1007/s00253-004-1787-z

    Article  CAS  PubMed  Google Scholar 

  57. Hsieh TC, Wu P, Park S, Wu JM (2006) Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity (PSP). BMC Complement Altern Med 6:30. doi:10.1186/1472-6882-6-30

    Article  PubMed  Google Scholar 

  58. Park YM, Won JH, Kim YH, Choi JW, Park HJ, Lee KT (2005) In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus. J Ethnopharmacol 101:120–128. doi:10.1016/j.jep.2005.04.003

    Article  PubMed  Google Scholar 

  59. Zhang Y, Mills GL, Nair MG (2003) Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita. Phytomedicine 10:386–390. doi:10.1078/0944-7113-00272

    Article  CAS  PubMed  Google Scholar 

  60. Jung CH, Jung H, Shin YC, Park JH, Jun CY, Kim HM, Yim HS, Shin MG, Bae HS, Kim SH, Ko SG (2007) Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage. J Ethnopharmacol 113:183–187. doi:10.1016/j.jep.2007.05.023

    Article  CAS  PubMed  Google Scholar 

  61. Ruimi N, Rwashdeh H, Wasser S, Konkimalla B, Efferth T, Borgatti M, Gambari R, Mahajna J (2009) Daedalea gibbosa substances inhibit LPS-induced expression of iNOS by suppression of NF-kappaB and MAPK activities in RAW 264.7 macrophage cells. Int J Mol Med 25:421–432. doi:10.3892/ijmm_00000361

    Google Scholar 

  62. Jin XY, Lee SH, Kim JY, Zhao YZ, Park EJ, Lee BS, Nan JX, Song KS, Ko G, Sohn DH (2006) Polyozellin inhibits nitric oxide production by down-regulating LPS-induced activity of NF-kappaB and SAPK/JNK in RAW 264.7 cells. Planta Med 72:857–859. doi:10.1055/s-2006-946640

    Article  CAS  PubMed  Google Scholar 

  63. Ren J, Chung SH (2007) Anti-inflammatory effect of alpha-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kappaB and mitogen-activated protein kinase pathways. J Agric Food Chem 55:5073–5080

    Article  CAS  PubMed  Google Scholar 

  64. Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR (2000) Act1, an NF-kappa B-activating protein. Proc Natl Acad Sci USA 97:10489–10493. doi:10.1073/pnas.160265197

    Article  CAS  PubMed  Google Scholar 

  65. Tanaka M, Fuentes ME, Yamaguchi K, Durnin MH, Dalrymple SA, Hardy KL, Goeddel DV (1999) Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice. Immunity 10:421–429

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was partly supported by the Ministry of Science and Technology of Israel, Grant No. 3-998 to JM.

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Authors and Affiliations

  1. Migal-Galilee Technology Center, Cancer Drug Discovery Program, P.O. Box 831, Kiryat Shmona, Israel

    Nili Ruimi, Roumyana D. Petrova, Sherbel Sussan & Jamal Mahajna

  2. International Center for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Mt. Carmel, 31905, Haifa, Israel

    Nili Ruimi, Roumyana D. Petrova & Solomon P. Wasser

  3. Department of Anatomy and Cell Biology, Faculty of Medicine, Technion, Haifa, Israel

    Roumyana D. Petrova & Abraham Z. Reznick

  4. Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Riad Agbaria

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  1. Nili Ruimi
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Correspondence to Jamal Mahajna.

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Nili Ruimi and Roumyana D. Petrova contributed equally to this work.

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Ruimi, N., Petrova, R.D., Agbaria, R. et al. Inhibition of TNFα-induced iNOS expression in HSV-tk transduced 9L glioblastoma cell lines by Marasmius oreades substances through NF-κB- and MAPK-dependent mechanisms. Mol Biol Rep 37, 3801–3812 (2010). https://doi.org/10.1007/s11033-010-0035-0

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