The nitrosylated flurbiprofen derivative HCT1026 inhibits cytokine-induced signalling through a novel mechanism of action

European Journal of Pharmacology

Volumn 602, Issue 2-3, 2009, Pages 215-222

  Idris, Aymen I ^a   Ralston, Stuart H ^a   van't Hof, Rob J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Cytokine; Inflammation; MAP kinase; NF B; Osteoclast

Indexed keywords

COLONY STIMULATING FACTOR 1; FLURBIPROFEN; FLURBIPROFEN 4 NITROXYBUTYL ESTER; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; NITRIC OXIDE; OSTEOCLAST DIFFERENTIATION FACTOR; SYNAPTOTAGMIN I; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL SURVIVAL; CYTOKINE PRODUCTION; DRUG MECHANISM; GASTROINTESTINAL SYMPTOM; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INHIBITION KINETICS; MACROPHAGE ACTIVATION; MOUSE; NITROSYLATION; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; PRIORITY JOURNAL; PROSTAGLANDIN SYNTHESIS INHIBITION;

ACTINS; ANIMALS; APOPTOSIS; BONE RESORPTION; CYTOKINES; ENZYME ACTIVATION; FLURBIPROFEN; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; NF-KAPPA B; NITROSO COMPOUNDS; OSTEOCLASTS; RANK LIGAND; SIGNAL TRANSDUCTION;

EID: 58149147147     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2008.11.023     Document Type: Article

References (39)

1. Afzal F., Polak J., and Buttery L. Endothelial nitric oxide synthase in the control of osteoblastic mineralizing activity and bone integrity. J. Pathol. 202 (2004) 503-510
2. Aguirre J., Buttery L., O'Shaughnessy M., Afzal F., Fernandez I D.M., Hukkanen M., Huang P., MacIntyre I., and Polak J. Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity. Am. J. Pathol. 158 (2001) 247-257
3. Ahmed S.A., Gogal Jr. R.M., and Walsh J.E. A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to [3H]thymidine incorporation assay. J. Immunol. Methods 170 (1994) 211-224
4. Anuar F., Whiteman M., Siau J.L., Kwong S.E., Bhatia M., and Moore P.K. Nitric oxide-releasing flurbiprofen reduces formation of proinflammatory hydrogen sulfide in lipopolysaccharide-treated rat. Br. J. Pharmacol. 147 (2006) 966-974
5. Armour K.E., Armour K.J., Gallagher M.E., Godecke A., Helfrich M.H., Reid D.M., and Ralston S.H. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 142 (2001) 760-766
6. Armour K.J., van't Hof R.J., Armour K.E., Torbergsen A.C., Del Soldato P., and Ralston S.H. Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone loss in vivo by flurbiprofen nitroxybutylester (HCT1026). Arthritis Rheum. 44 (2001) 2185-2192
7. Asagiri M., and Takayanagi H. The molecular understanding of osteoclast differentiation. Bone 40 (2007) 251-264
8. Bernardo A., Ajmone-Cat M.A., Gasparini L., Ongini E., and Minghetti L. Nuclear receptor peroxisome proliferator-activated receptor-gamma is activated in rat microglial cells by the anti-inflammatory drug HCT1026, a derivative of flurbiprofen. J. Neurochem. 92 (2005) 895-903
9. Bernardo A., Gasparini L., Ongini E., and Minghetti L. Dynamic regulation of microglial functions by the non-steroidal anti-inflammatory drug NCX 2216: implications for chronic treatments of neurodegenerative diseases. Neurobiol. Dis. 22 (2006) 25-32
10. Brandi M.L., Hukkanen M., Umeda T., Moradi-Bidhendi N., Bianchi S., Gross S.S., Polak J.M., and MacIntyre I. Bidirectional regulation of osteoclast function by nitric oxide synthase isoforms. Proc. Natl. Acad. Sci. USA. 92 (1995) 2954-2958
11. Carmody R.J., and Chen Y.H. Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. Cell Mol. Immunol. 4 (2007) 31-41
12. Cicala C., Ianaro A., Fiorucci S., Calignano A., Bucci M., Gerli R., Santucci L., Wallace J.L., and Cirino G. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis. Br. J. Pharmacol. 130 (2000) 1399-1405
13. Davies N.M., Roseth A.G., Appleyard C.B., McKnight W., Del Soldato P., Calignano A., Cirino G., and Wallace J.L. NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects. Aliment. Pharmacol. Ther. 11 (1997) 69-79
14. Forwood M.R. Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J. Bone Miner. Res. 11 (1996) 1688-1693
15. Franzoso G., Carlson L., Xing L., Poljak L., Shores E.W., Brown K.D., Leonardi A., Tran T., Boyce B.F., and Siebenlist U. Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev. 11 (1997) 3482-3496
16. Fratelli M., Minto M., Crespi A., Erba E., Vandenabeele P., Del Soldato P., and Ghezzi P. Inhibition of nuclear factor-kappaB by a nitro-derivative of flurbiprofen: a possible mechanism for antiinflammatory and antiproliferative effect. Antioxid. Redox. Signal. 5 (2003) 229-235
17. Gingery A., Bradley E., Shaw A., and Oursler M.J. Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFkappaB pathways to maintain osteoclast survival. J. Cell Biochem. 89 (2003) 165-179
18. Grigoriadis A.E., Wang Z.Q., Cecchini M.G., Hofstetter W., Felix R., Fleisch H.A., and Wagner E.F. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266 (1994) 443-448
19. Idris A.I., Del Soldato P., Ralston S.H., and van't Hof R.J. The flurbiprofen derivatives HCT1026 and HCT1027 inhibit bone resorption by a mechanism independent of COX inhibition and nitric oxide production. Bone 35 (2004) 636-643
20. Iotsova V., Caamano J., Loy J., Yang Y., Lewin A., and Bravo R. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat. Med. 3 (1997) 1285-1289
21. Jimi E., Nakamura I., Ikebe T., Akiyama S., Takahashi N., and Suda T. Activation of NF-kappaB is involved in the survival of osteoclasts promoted by interleukin-1. J. Biol. Chem. 273 (1998) 8799-8805
22. Kawaguchi H., Pilbeam C.C., Harrison J.R., and Raisz L.G. The role of prostaglandins in the regulation of bone metabolism. Clin. Orthop. Relat. Res. (1995) 36-46
23. Klein-Nulend J., Semeins C.M., Ajubi N.E., Nijweide P.J., and Burger E.H. Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts-correlation with prostaglandin upregulation. Biochem. Biophys. Res. Commun. 217 (1995) 640-648
24. Lee S.E., Chung W.J., Kwak H.B., Chung C.H., Kwack K.B., Lee Z.H., and Kim H.H. Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J. Biol. Chem. 276 (2001) 49343-49349
25. Li X., Okada Y., Pilbeam C.C., Lorenzo J.A., Kennedy C.R., Breyer R.M., and Raisz L.G. Knockout of the murine prostaglandin EP2 receptor impairs osteoclastogenesis in vitro. Endocrinology 141 (2000) 2054-2061
26. Miyazaki T., Katagiri H., Kanegae Y., Takayanagi H., Sawada Y., Yamamoto A., Pando M.P., Asano T., Verma I.M., Oda H., Nakamura K., and Tanaka S. Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. J. Cell Biol. 148 (2000) 333-342
27. Mizukami J., Takaesu G., Akatsuka H., Sakurai H., Ninomiya-Tsuji J., Matsumoto K., and Sakurai N. Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6. Mol. Cell Biol. 22 (2002) 992-1000
28. Ono K., Akatsu T., Murakami T., Kitamura R., Yamamoto M., Shinomiya N., Rokutanda M., Sasaki T., Amizuka N., Ozawa H., Nagata N., and Kugai N. Involvement of cyclo-oxygenase-2 in osteoclast formation and bone destruction in bone metastasis of mammary carcinoma cell lines. J. Bone Miner. Res. 17 (2002) 774-781
29. Roodman G.D. Regulation of osteoclast differentiation. Ann. N.Y. Acad. Sci. 1068 (2006) 100-109
30. Takayanagi H., Kim S., Koga T., Nishina H., Isshiki M., Yoshida H., Saiura A., Isobe M., Yokochi T., Inoue J., Wagner E.F., Mak T.W., Kodama T., and Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell 3 (2002) 889-901
31. Tegeder I., Niederberger E., Israr E., Guhring H., Brune K., Euchenhofer C., Grosch S., and Geisslinger G. Inhibition of NF-kappaB and AP-1 activation by R- and S-flurbiprofen. FASEB J. 15 (2001) 595-597
32. van't Hof R.J. Osteoclast formation in the mouse co-culture assay. Methods Mol. Med. 80 (2003) 145-152
33. van't Hof R.J., and Ralston S.H. Cytokine-induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J. Bone Miner. Res. 12 (1997) 1797-1804
34. van't Hof R.J., and Ralston S.H. Nitric oxide and bone. Immunology 103 (2001) 255-261
35. van't Hof R.J., Armour K.J., Smith L.M., Armour K.E., Wei X.Q., Liew F.Y., and Ralston S.H. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. Proc. Natl. Acad. Sci. U.S.A 97 (2000) 7993-7998
36. van't Hof R.J., Macphee J., Libouban H., Helfrich M.H., and Ralston S.H. Regulation of bone mass and bone turnover by neuronal nitric oxide synthase. Endocrinology 145 (2004) 5068-5074
37. Wallace J.L., and Del Soldato P. The therapeutic potential of NO-NSAIDs. Fundam. Clin. Pharmacol. 17 (2003) 11-20
38. Wallace J.L., Muscara M.N., de Nucci G., Zamuner S., Cirino G., Del Soldato P., and Ongini E. Gastric tolerability and prolonged prostaglandin inhibition in the brain with a nitric oxide-releasing flurbiprofen derivative, NCX-2216 [3-[4-(2-fluoro-alpha-methyl-[1,1′-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester]. J. Pharmacol. Exp. Ther. 309 (2004) 626-633
39. Wallace J.L., Reuter B., Cicala C., McKnight W., Grisham M.B., and Cirino G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology 107 (1994) 173-179