RINGRAZIAMENTI
La ricerca presuppone un lavoro di squadra e pertanto, a conclusione della mia Tesi di Laurea, sento di dover ringraziare tutti coloro che, a vario titolo, ne hanno reso possibile la realizzazione.
Un riconoscente grazie alla Prof.ssa Anna Maria Bianucci e alla Prof.ssa Irene Giorgi per l'opportunità formativa che mi hanno offerto proponendomi un interessante argomento di ricerca.
Un sentito grazie alla Dott.ssa Alice Borghini e al Dott. Daniele Pietra per la disponibilità, per la collaborazione, per il costante supporto tecnico-scientifico durante i mesi di lavoro insieme, per l'entusiasmo e la passione per la ricerca che mi hanno trasmesso.
Ringrazio anche i ragazzi del laboratorio Santina, Carmine e Marco per la loro collaborazione.
Ringrazio infine il Prof. Giuseppe Lubinu ed il Dott. Pierluigi Madau del Dipartimento di Chimica e Farmacia - Università di Sassari per l’esecuzione degli esperimenti HPLC successivamente analizzati nel nostro laboratorio.
I finanziamenti utilizzati per la ricerca descritta in questa tesi sono stati resi disponibili dalla International Society for Drug Development (ISDD) S.p.A. (Milano) attraverso un contratto di collaborazione stipulato con il Dipartimento di Farmacia – Università di Pisa.
ACRONIMI
AcP: accessory protein
ASK1: Apoptosis Signal-regulating Kinase 1 COX: ciclossigenasi
DAG: diacilglicerolo
DPPH: 2,2-difenil-1-picrilidrazile ECM: matrice extracellulare
EGF (Epidermal Growth Factor): fattore della crescita epidermica ERK: Extracellular signal-Regulated Kinase
FADD: Fas-Associated Death Domain
FGF(Fibroblast Growth Factor): fattori della crescita derivanti dai fibroblasti GDP : guanosina difosfato
GEF: guanine nucleotide exchange factor
GlyCam: Glycosylation-dependent Cell adhesion molecule 1
GM-CSF (Granulocyte Macrophage Colony-Stimulating Factor): fattore stimolante le
colonie granulocitarie-macrofagiche
GRK: G protein-coupled Receptor Kinase GRO-α: Growth-Related Oncogene-α GTP: guanosina trifosfato
HDF: Human Dermal Fibroblast
5-HETE: acido 5-idrossieicosantetraenico 5-HPETE: acido5-idroperossieicosantetraenico HRP: enzima perossidasi di rafano
Hsp90: Heat shock protein 90
ICAM-1/2: Intercellular Adhesion Molecule-1/2 IFNγ: interferone γ
IGF (Insuline like Growth Factor): fattore della crescita insulino simile IgG: immunoglobulina G
IgM: immunoglobulina M
I-κB: Inhibitory counterparts of the NfκB IKK: I-κB Kinase
IL-1: interleuchina 1 IL-6: interleuchina 6 IL-8: interleuchina 8
IP-10: Interferon-γ-inducible Protein-10 IP3: inositolo-1,4,5-trifosfato
IP-3K: fosfatidilinositolo-3-chinasi IRAK: IL-1 Receptor Activated Kinase JNK: c-Jun N-terminal Kinase
LTA4: leucotriene A4
LTB4 : leucotriene B4
LTC4 : leucotriene C4
LTD4 : leucotriene D4
LTE2 : leucotriene E2
MAC: complesso di attacco alla membrana
MadCam: Mucosal vascular addressin Cell adhesion molecule 1
MAPK (Mitogen Activated Protein Kinase): protein chinasi attivate da mitogeni MAPKKK: MAP Kinase Kinase Kinase
MCP-1: Monocyte Chemoattractant Protein-1 MEK: Mitogen activated protein kinase/Erk Kinase
MEKK3: Mitogen Activated protein Kinase/Erk Kinase kinase 3 MKK6: MAPK Kinase 6
MMP: metalloproteasi
MyD88: Myeloid Differentiation primary response gene 88 NADPH: nicotinammide adenina dinucleotide fosfato NEMO: NFκB Essential Modulator
NFκB: Nuclear Factor kappa B PAF: fattore attivante le piastrine
PDGF (Platelet Derived Growth Factor): fattore della crescita derivante dalle piastrine PECAM-1: Platelet Endothelial Cell-Adhesion Molecule
PGD2: prostaglandina D2
PGE2 : prostaglandina E2
PGH2: prostaglandina H2
PIP2: fosfatidilinositolo-4,5-bifosfato
PKC: protein chinasi C
PSGL-1: P-Selectine Glycoprotein Ligand-1 PSR: Picro-Sirius Red
RIP: Receptor Interacting Protein ROS: specie reattive dell’ossigeno
Smad: Small mother against decapentaplegic SOD: superossido dismutasi
STAT: Signal Transducer and Activator of Transcription TAB2: TGF-β Activated kinase/MAP3K7 Binding protein 2 TAK1: TGF-β Activated Kinase 1
TGF-α (Trasforming Growth Factor α): fattore di crescita trasformante-α TGF-β (Trasforming Growth Factor β): fattore di crescita trasformante-β TNFα (Tumor necrosis factor-α): fattore di necrosi tumorale α
Tollip: Toll interacting protein
TRADD: TNF Receptor-Associated Death Domain protein TRAF2: TNF Receptor-Associated Factor 2
TRAF6: TNF Receptor Associated Factor 6 TRL: Toll-Like Receptor
TXA2: trombossano A2
VCAM-1:Vascular Cell Adhesion Molecule-1
BIBLIOGRAFIA
T. Velnar, T. Bailey, V. Smrkolj The Journal of International Medical Research 2009; 37: 1528 – 1542
Pasqualino, Panattoni Anatomia Umana UTET 2002
Sabine Werner, Richard Grose Physiol. Rev. 2003; 83: 835–870 Oliver Wertz Planta Med 2007;73: 1331-1357
Qin Hu, Mazhar Noor1 Nephrol Dial Transplant (2009) 24: 3033–3041
Jack W Penn, Adriaan O Grobbelaar, Kerstin J Rolfe Int J Burn Trauma 2012;2(1):18-28 Ehrhardt Proksch, Johanna M. Brandner, Jens-Michael Jensen Experimental Dermatology 2008; 17: 1063–1072
Sashwati Roy, Savita Khanna, Kishore Nallu, Thomas K. Hunt, Chandan K. Sen Mol.
Ther. January 2006 ; 13(1): 211–220
Katerina Oikonomopoulou, Daniel Ricklin, Peter A. Ward, Jhon D. Lambris Semin.
Immunophatol. January 2012; 34(1): 151-165
Adam Freund, Arturo V. Orjalo, Pierre-Yves Desprez, Judith Campisi Trends Mol. Med. 2010 May; 16(5): 238–246
Qin M. Chen, James C. Bartholomew, Judith Campis, Meileen Acosta, Joshua D. Reagan, Bruce N. Ames Biochem. J. 1998; 332: 43-50
Paoletti, Nicosia, Clementi, Fumagalli Farmacologia generale e molecolare UTET terza edizione, 2004
Singer AJ, Clark RA. N Engl J Med 1999; 341: 738-746
Wang R, Ghahary A, Shen Q, Scott PG, Roy K,Tredget EE. Wound Repair Regen 2000; 8: 128-137
Schmid P, Itin P, Cherry G, Bi C, Cox DA. Am J Pathol 1998; 152: 485-493 Latha Satish and Sandeep Kathju Volume 2010, Article ID 790234, 11 pages
Theresa C. Barnes,Marina E. Anderson, and Robert J.Moots International Journal of
Rheumatology Volume 2011, Article ID 721608, 6 pages
Kyung-A Hwang, Bo-Rim Yi, Kyung-Chul Choi Lab. Anim. Res. 2011; 27(1): 1-8
Jaspers, Thomas Blatt, Klaus-Peter Wittern, Horst Wenck, Josef A. Kas Biophysical
Journal 2010; 99: 2434–2442
Hiroaki Iwasa, Jiahuai Han, Fuyuki Ishikawa Genes to Cells 2003; 8: 131–144
Eunsung Junn, Kee Nyung Lee, Hyang Ran Ju, Seung Hyun Han, Joo Young Im, Hyung Sik Kang, Tae Ho Lee, Yun Soo Bae, Kwon Soo Ha, Zee Won Lee, Sue Goo Rhee, Inpyo Choi J. Immunol. 2000; 165: 2190-2197
Jiří Kanta ACTA MEDICA (Hradec Králové) 2011; 54(3): 97–101 Chandan K. Wound Repair Regen 2009 ; 17(1): 1–18
Qihe Xu, Jill T. Norman, Shashi Shrivastav, Javier Lucio-Cazana, Jeffrey B.Kopp Am J.
Physiol Renal Physiol 2007; 293: F631-F640
Robbins Le basi patologiche delle malattie PICCIN sesta edizione, 2000
R. Singh, B. Wang, A. Shirvaikar, S. Khan, S. Kamat, J.R. Schelling, M. Konieczkowski, J.R. Sedor The Journal of Clinical Investigation 1999; 103: 1561-1570
Lanny J. Rosenwasser J. Allergy Clin. Immunol. September 1998; 344-350 V.K. Garg, S. K. Paliwal J. Adv Pharm. Technol. Res. 2011; 2(2): 110–114. Gu et al.Journal of Separation Science. 2010; 33: 1004-1009
A.P.M. Bernardi, C. Lòpez-Alarcòn, A. Aspee, S. Rech, G.L. Von Poser, R. Bride, E. Lissp J. Chil. Chem. Soc. 2007; 52: 1326-1329
Paul J. Davis Wounds UK, 2008; vol. 4, N°4
Monique E Cho, Jeffrey B Kopp Expert Opin Investig Drugs, 2010 February; 19(2): 275– 283.
Jack W Penn, Adriaan O Grobbelaar, Kerstin J Rolfe Int J Burn Trauma 2012; 2(1): 18-28 Theresa Barnes,Marina Anderson, Robert Moots International Journal of Rheumatology
Volume 2011, Article ID 721608
Qin Hu, Mazhar Noor, Yuen Fei Wong, Peter J. Hylands, Monique S. J. Simmonds, Qing Xu,Dan Jiang, Bruce M. Hendry, Qihe Xu Nephrol Dial Transplant 2009; 24: 3033–3041 Christine E. Pullar, R. Rivkah Isseroff Journal of Cell Science 2005;118: 2023-2034 Regina M. DayYuichiro, J. Suzuki Dose-Response 2005; 3: 425–442
Marilena Gilca, Laura Gaman, Elena Panait, Irina Stoian, Valeriu Atanasiu Forsch
Chatanya S. Nirodi, Radika Devalaraja, Lillian B. Nanney, Saundrett Arrindell, Shirley Russell, Joel Trupin, Ann Richmond Wound Repair Regen 2000 ; 8(5): 371–382
Björn Petri, M. Gabriele Bixel FEBS Journal 2006; 273: 4399-4407
Eva Engelhardt, Atiye Toksoy, Matthias Goebeler, Sebastian Debus, Eva-Bettina Brocker, Reinhard Gillitzer American Journal of Pathology Vol. 153, No. 6
Reinhard Gillitzer, Matthias Goebeler Journal of Leukocyte Biology 2001, vol. 69
Zi-Qing Lin, Toshikazu Kondo, Yuko Ishida, Tatsunori Takayasu, Naofumi Mukaida Journal of Leukocyte Biology 2003,vol. 73
David M. Mosser, Justin P. Edwards Nat. Rev. Immunol. 2008 December ; 8(12): 958–969 Laetitia Sabatier, Daliang Chen, Christine Fagotto-Kaufmann, Dirk Hubmacher, Marc McKee, Douglas S. Annis, Deane F. Mosher, Dieter P. Reinhardt Molecular Biology of the
Cell 2009; 20: 846–858
H. Wajant, K. Pfizenmaier, P. Scheurich Cell Death and Differentiation 2003; 10: 45-65 Abdoelwaheb El Ghalbzouri, Paul Hensbergen, Sue Gibbs, Johanna Kempenaar, Roel van der Schors, Maria Ponec Laboratory Investigation 2004; 84: 102–112
S.J. Flavell, T.Z. Hou, S. Lax, A.D. Filer, M. Salmon, C.D. Buckley British Journal of
Pharmacology 2008; 153: S241–S246
Helen M. McGettrick, Emily Smith, Andrew Filer, Stephen Kissane, Michael Salmon, Christopher D. Buckley, G. Ed Rainger, Gerard B. Nash Eur. J. Immunol. 2009; 39: 113– 125
Adam W. Studebaker, Gianluca Storci, Jillian L. Werbeck, et al. Cancer Res 2008; 68: 9087-9095
Francesca Levi-Schaffer, Ekaterina Garbuzenko, Ann Rubin, Reuven Reich, Dalia Pickholz, Philippe Gillery, Herve Emonard, Arnon Nagler, Francois A. Xavier Maquart
Cell Biology 1999; 96: 9660–9665
Qihe Xu, Jill T. Norman, Shashi Shrivastav, Javier Lucio-Cazana, Jeffrey B. Kopp Am J.
Physiol Renal Physiol 2007; 293: F631–F640
Meinhard Schiller, Sylviane Dennler, Ulf Anderegg, Agatha Kokot, Jan C. Simon, Thomas A. Luger, Alain Mauviel, Markus Bohm The Journal of Biological Chemistry 2010; 285(1): 409–421
Kenneth Kaushansky, Nancy Lin, John W.Adamson J.Clin.Invest. 1998; 81: 92-97
Tohru Akahoshi, Joost J.Oppenheim, Kouji Matsushima The Journal of Clinical
Investigation 1988; 82: 1219-1224
Randle M. Gallucci, Dusti K. Sloan, Julie M. Heck, Anne R. Murray, Sijy J. O’Dell J.
Sabine Werner, Thomas Krieg, Hans Smola Journal of Investigative Dermatology 2007; 127: 998–1008
Justin P. Annes, John S. Munger, Daniel B Rifkin Journal of Cell Science 2003;116: 217-224
Wei Li, Jianhua Fan, Mei Chen, Shengxi Guan, David Sawcer, Gary M. Bokoch, David T. Woodley Molecular Biology of the Cell 2004; 15: 294–309
Song Li, Ngan F. Huang, Steven Hsu Journal of Cellular Biochemistry 2005; 96:1110– 1126
Jason R. Chan, Sharon J. Hyduk, Myron I. Cybulsky Journal of Immunological Methods 2003; 273: 43-52
Danielle T. Loughlin, Carol M. Artlett PLoS ONE May 2011; Issue 5 ,Volume 6
Chandan K. Sen, Sashwati Roy Biochim Biophys Acta 2008 November; 1780(11): 1348– 1361
Sarkozi A. et al. Chromatographia 2006; 63: S81-S86
Andrew Bowie, Luke A.J. O’Neill Journal of Leukocyte Biology April 2000;67: 508-514 Han Chung Chong, Ming Jie Tan, Virginie Philippe, Siew Hwey Tan, Chek Kun Tan, Chee Wai Ku, Yan Yih Goh, Walter Wahli, Liliane Michalik, Nguan Soon Tan J. Cell Biol. Vol. 184; No. 6 : 817–831
Christiane Amendt, Amrit Mann, Peter Schirmacher, Manfred Blessing Journal of Cell
Science 2002; 115: 2189-2198
Christopher P. Kiritsy, Samuel E. Lynch Critical Reviews in Oral Biology and Medicine 1993; 4(5): 729-760
Mathieu P. Rodero, Kiarash Khosrotehrani Int. J. Clin. Exp. Pathol. 2010; 3(7): 643-653 Christophe Frippiat, Qin M. Chen, Stephanie Zdanov, Joao-Padro Magalhaes, Jose Remacle, Olivier Toussaint The Journal of Biological Chemistry 2001; 276(4): 2531–2537 Brian K. Pilcher, Jo Ann Dumin, Barry D. Sudbeck, Stephen M. Krane, Howard G. Welgus, William C. Parks The Journal of Cell Biology 1997; 137(6): 1445–1457
Ran You, Mingzhe Zheng, Paula J. McKeown-Longo The Journal of Biological Chemistry 2010; 285(47): 36255-36259
Michael U. Martin, Holger Wesche Biochimica et Biophysica Acta 2002; 1592: 265-280 Dolores Pérez-Sala, Angelita Rebollo Cell Death and Differentiation 1999; 6: 722-728 Adewale Adetutu, Winston A. Morgan, Olivia Corcoran Journal of Ethnopharmacology
Jeremi S. Mullins, Larry G. Arlian, Marjorie S. Morgan J. Med. Entomol. 2009 July; 46(4): 845–851
Tamsyn S.A .Thring, Pauline Hili, Declan P. Naughton Journal of Inflammation 2011; 8:27 Nuno Rainha, Elisabete Lima, José Baptista, Carolina Rodrigues Journal of Medicinal
Plants Research 2011; 5(10): 1930-1940
Ayoub Rashid, M. Zahid Qureshi, Syed Ali Raza, J. William, M. Arshad Analele
