Skip to main content
Top
Published in: Journal of Inflammation 1/2012

Open Access 01-12-2012 | Research

Apoptosis inhibition or inflammation: the role of NAIP protein expression in Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node

Authors: Safoura Mazrouei, Amin Ziaei, Amir Pouya Tanhaee, Kianoosh Keyhanian, Mahdad Esmaeili, Azar Baradaran, Mansoor Salehi

Published in: Journal of Inflammation | Issue 1/2012

Login to get access

Abstract

Background

Inhibitors of Apoptosis (IAP) family play a critical role in apoptosis and inflammatory response. Neuronal Apoptosis Inhibitory Protein (NAIP), as a member of both IAPs and NLR families (NOD-Like Receptor), is a unique IAP harboring NOD (Nucleotide Oligomerization Domain) and LLR (Leucine Rich Repeat) motifs. Considering these motifs in NAIP, it has been suggested that the main function of NAIP is distinct from other members of IAPs. As a member of NLR, NAIP mediates the assembly of 'Inflammasome' for inflammatory caspase activation. Pathologic expression of NAIP has been reported not only in some infectious and inflammatory diseases but also in some malignancies. However, there is no report to elucidate NAIP expression in lymphomatic malignancies.

Methods

In this study, we examined NAIP protein expression in 101 Formalin-Fixed Paraffin-Embedded blocks including samples from 39 Hodgkin Lymphoma and 23 Non Hodgkin Lymphoma cases in comparison with 39 control samples (30 normal and 9 Reactive Lymphoid Hyperplasia (RLH) lymph nodes) using semi-quantitative immuno-flourecent Staining.

Results

NAIP expression was not statistically different in lymphoma samples neither in HL nor in NHL cases comparing to normal samples. However, we evaluated NAIP expression in normal and RLH lymph nodes. Surprisingly, we have found a statistically significant-difference between the NAIP expression in RLH (M.R of NAIP/GAPDH expression = 0.6365 ± 0.017) and normal lymph node samples (M.R of NAIP/GAPDH expression = 0.5882 ± 0.047) (P < 0.01).

Conclusions

These findings show that the regulation of apoptosis could not be the main function of NAIP in the cell, so the pathologic expression of NAIP is not involved in lymphoma. But, we concluded that the over expression of NAIP has more effective role in the inflammatory response. Also, this study clarifies the NAIP expression level in lymphoma which is required for IAPs profiling in order to be used in potential translational applications of IAPs.
Appendix
Available only for authorised users
Literature
1.
go back to reference Nachmias B, Ashhab Y, Ben-Yehuda D: The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. Semin Cancer Biol. 2004, 14: 231-243. 10.1016/j.semcancer.2004.04.002.CrossRefPubMed Nachmias B, Ashhab Y, Ben-Yehuda D: The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. Semin Cancer Biol. 2004, 14: 231-243. 10.1016/j.semcancer.2004.04.002.CrossRefPubMed
2.
go back to reference Herman MD, Moche M, Flodin S, Welin M, Tresaugues L, Johansson I, Nilsson M, Nordlund P, Nyman T: Structures of BIR domains from human NAIP and cIAP2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009, 65: 1091-1096. 10.1107/S1744309109038597.PubMedCentralCrossRefPubMed Herman MD, Moche M, Flodin S, Welin M, Tresaugues L, Johansson I, Nilsson M, Nordlund P, Nyman T: Structures of BIR domains from human NAIP and cIAP2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009, 65: 1091-1096. 10.1107/S1744309109038597.PubMedCentralCrossRefPubMed
3.
go back to reference Karimpour S, Davoodi J, Ghahremani MH: Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP. Biochem Biophys Res Commun. 2011, 407: 158-162. 10.1016/j.bbrc.2011.02.130.CrossRefPubMed Karimpour S, Davoodi J, Ghahremani MH: Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP. Biochem Biophys Res Commun. 2011, 407: 158-162. 10.1016/j.bbrc.2011.02.130.CrossRefPubMed
4.
go back to reference Davoodi J, Ghahremani MH, Es-Haghi A, Mohammad-Gholi A, Mackenzie A: Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9. Int J Biochem Cell Biol. 2010, 42: 958-964. 10.1016/j.biocel.2010.02.008.CrossRefPubMed Davoodi J, Ghahremani MH, Es-Haghi A, Mohammad-Gholi A, Mackenzie A: Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9. Int J Biochem Cell Biol. 2010, 42: 958-964. 10.1016/j.biocel.2010.02.008.CrossRefPubMed
5.
go back to reference Liston P, Fong WG, Korneluk RG: The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene. 2003, 22: 8568-8580. 10.1038/sj.onc.1207101.CrossRefPubMed Liston P, Fong WG, Korneluk RG: The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene. 2003, 22: 8568-8580. 10.1038/sj.onc.1207101.CrossRefPubMed
6.
go back to reference Jantas D, Lorenc-Koci E, Kubera M, Lason W: Neuroprotective effects of MAPK/ERK1/2 and calpain inhibitors on lactacystin-induced cell damage in primary cortical neurons. Neurotoxicology. 2011, 32 (6): 845-856. 10.1016/j.neuro.2011.05.013. Epub 2011 Jun 1CrossRefPubMed Jantas D, Lorenc-Koci E, Kubera M, Lason W: Neuroprotective effects of MAPK/ERK1/2 and calpain inhibitors on lactacystin-induced cell damage in primary cortical neurons. Neurotoxicology. 2011, 32 (6): 845-856. 10.1016/j.neuro.2011.05.013. Epub 2011 Jun 1CrossRefPubMed
7.
go back to reference de Graaf AO, van Krieken JH, Tonnissen E, Wissink W, van de Locht L, Overes I, Dolstra H, de Witte T, van der Reijden BA, Jansen JH: Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies. Br J Haematol. 2005, 130: 852-859. 10.1111/j.1365-2141.2005.05690.x.CrossRefPubMed de Graaf AO, van Krieken JH, Tonnissen E, Wissink W, van de Locht L, Overes I, Dolstra H, de Witte T, van der Reijden BA, Jansen JH: Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies. Br J Haematol. 2005, 130: 852-859. 10.1111/j.1365-2141.2005.05690.x.CrossRefPubMed
8.
go back to reference Grzybowska-Izydorczyk O, Cebula B, Robak T, Smolewski P: Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia. Eur J Cancer. 2010, 46: 800-810. 10.1016/j.ejca.2009.11.023.CrossRefPubMed Grzybowska-Izydorczyk O, Cebula B, Robak T, Smolewski P: Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia. Eur J Cancer. 2010, 46: 800-810. 10.1016/j.ejca.2009.11.023.CrossRefPubMed
9.
go back to reference Choi J, Hwang YK, Sung KW, Lee SH, Yoo KH, Jung HL, Koo HH, Kim HJ, Kang HJ, Shin HY, Ahn HS: Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood. 2007, 109: 471-477. 10.1182/blood-2006-07-032557.CrossRefPubMed Choi J, Hwang YK, Sung KW, Lee SH, Yoo KH, Jung HL, Koo HH, Kim HJ, Kang HJ, Shin HY, Ahn HS: Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood. 2007, 109: 471-477. 10.1182/blood-2006-07-032557.CrossRefPubMed
10.
go back to reference Choi J, Hwang YK, Choi YJ, Yoo KE, Kim JH, Nam SJ, Yang JH, Lee SJ, Yoo KH, Sung KW, et al.: Neuronal apoptosis inhibitory protein is overexpressed in patients with unfavorable prognostic factors in breast cancer. J Korean Med Sci. 2007, 22 (Suppl): S17-S23. 10.3346/jkms.2007.22.S.S17.PubMedCentralCrossRefPubMed Choi J, Hwang YK, Choi YJ, Yoo KE, Kim JH, Nam SJ, Yang JH, Lee SJ, Yoo KH, Sung KW, et al.: Neuronal apoptosis inhibitory protein is overexpressed in patients with unfavorable prognostic factors in breast cancer. J Korean Med Sci. 2007, 22 (Suppl): S17-S23. 10.3346/jkms.2007.22.S.S17.PubMedCentralCrossRefPubMed
11.
go back to reference Schlette EJ, Medeiros LJ, Goy A, Lai R, Rassidakis GZ: Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma. J Clin Oncol. 2004, 22: 1682-1688. 10.1200/JCO.2004.10.172.CrossRefPubMed Schlette EJ, Medeiros LJ, Goy A, Lai R, Rassidakis GZ: Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma. J Clin Oncol. 2004, 22: 1682-1688. 10.1200/JCO.2004.10.172.CrossRefPubMed
12.
go back to reference Grzybowska-Izydorczyk O, Smolewski P: The role of the inhibitor of apoptosis protein (IAP) family in hematological malignancies. Postepy Hig Med Dosw (Online). 2008, 62: 55-63. Grzybowska-Izydorczyk O, Smolewski P: The role of the inhibitor of apoptosis protein (IAP) family in hematological malignancies. Postepy Hig Med Dosw (Online). 2008, 62: 55-63.
13.
go back to reference Wang L, Zhang Q, Liu B, Han M, Shan B: Challenge and promise: roles for Livin in progression and therapy of cancer. Mol Cancer Ther. 2008, 7: 3661-3669. 10.1158/1535-7163.MCT-08-0480.CrossRefPubMed Wang L, Zhang Q, Liu B, Han M, Shan B: Challenge and promise: roles for Livin in progression and therapy of cancer. Mol Cancer Ther. 2008, 7: 3661-3669. 10.1158/1535-7163.MCT-08-0480.CrossRefPubMed
14.
go back to reference Kasof GM, Gomes BC: Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem. 2001, 276: 3238-3246. 10.1074/jbc.M003670200.CrossRefPubMed Kasof GM, Gomes BC: Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem. 2001, 276: 3238-3246. 10.1074/jbc.M003670200.CrossRefPubMed
15.
go back to reference Verhagen AM, Coulson EJ, Vaux DL: Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol. 2001, 2 (7): REVIEWS3009-Epub 2001 Jul 5PubMedCentralCrossRefPubMed Verhagen AM, Coulson EJ, Vaux DL: Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol. 2001, 2 (7): REVIEWS3009-Epub 2001 Jul 5PubMedCentralCrossRefPubMed
16.
go back to reference Schimmer AD: Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. 2004, 64: 7183-7190. 10.1158/0008-5472.CAN-04-1918.CrossRefPubMed Schimmer AD: Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. 2004, 64: 7183-7190. 10.1158/0008-5472.CAN-04-1918.CrossRefPubMed
17.
go back to reference Dubrez-Daloz L, Dupoux A, Cartier J: IAPs: more than just inhibitors of apoptosis proteins. Cell Cycle. 2008, 7: 1036-1046. 10.4161/cc.7.8.5783.CrossRefPubMed Dubrez-Daloz L, Dupoux A, Cartier J: IAPs: more than just inhibitors of apoptosis proteins. Cell Cycle. 2008, 7: 1036-1046. 10.4161/cc.7.8.5783.CrossRefPubMed
18.
go back to reference Yan B: Research progress on Livin protein: an inhibitor of apoptosis. Mol Cell Biochem. 2011, 357 (1-2): 39-45. 10.1007/s11010-011-0873-7. Epub 2011 May 27CrossRefPubMed Yan B: Research progress on Livin protein: an inhibitor of apoptosis. Mol Cell Biochem. 2011, 357 (1-2): 39-45. 10.1007/s11010-011-0873-7. Epub 2011 May 27CrossRefPubMed
19.
go back to reference Maier JK, Lahoua Z, Gendron NH, Fetni R, Johnston A, Davoodi J, Rasper D, Roy S, Slack RS, Nicholson DW, MacKenzie AE: The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci. 2002, 22: 2035-2043.PubMed Maier JK, Lahoua Z, Gendron NH, Fetni R, Johnston A, Davoodi J, Rasper D, Roy S, Slack RS, Nicholson DW, MacKenzie AE: The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci. 2002, 22: 2035-2043.PubMed
20.
go back to reference Chamaillard M, Girardin SE, Viala J, Philpott DJ: Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation. Cell Microbiol. 2003, 5: 581-592. 10.1046/j.1462-5822.2003.00304.x.CrossRefPubMed Chamaillard M, Girardin SE, Viala J, Philpott DJ: Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation. Cell Microbiol. 2003, 5: 581-592. 10.1046/j.1462-5822.2003.00304.x.CrossRefPubMed
21.
go back to reference Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G: The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009, 10: 241-247.PubMedCentralCrossRefPubMed Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G: The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009, 10: 241-247.PubMedCentralCrossRefPubMed
22.
go back to reference Maier JK, Balabanian S, Coffill CR, Stewart A, Pelletier L, Franks DJ, Gendron NH, MacKenzie AE: Distribution of neuronal apoptosis inhibitory protein in human tissues. J Histochem Cytochem. 2007, 55: 911-923. 10.1369/jhc.6A7144.2007.CrossRefPubMed Maier JK, Balabanian S, Coffill CR, Stewart A, Pelletier L, Franks DJ, Gendron NH, MacKenzie AE: Distribution of neuronal apoptosis inhibitory protein in human tissues. J Histochem Cytochem. 2007, 55: 911-923. 10.1369/jhc.6A7144.2007.CrossRefPubMed
23.
go back to reference Martinon F, Tschopp J: Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007, 14: 10-22. 10.1038/sj.cdd.4402038.CrossRefPubMed Martinon F, Tschopp J: Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007, 14: 10-22. 10.1038/sj.cdd.4402038.CrossRefPubMed
24.
go back to reference Martinon F, Gaide O, Petrilli V, Mayor A, Tschopp J: NALP inflammasomes: a central role in innate immunity. Semin Immunopathol. 2007, 29: 213-229. 10.1007/s00281-007-0079-y.CrossRefPubMed Martinon F, Gaide O, Petrilli V, Mayor A, Tschopp J: NALP inflammasomes: a central role in innate immunity. Semin Immunopathol. 2007, 29: 213-229. 10.1007/s00281-007-0079-y.CrossRefPubMed
25.
go back to reference Ting JP, Davis BK: CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol. 2005, 23: 387-414. 10.1146/annurev.immunol.23.021704.115616.CrossRefPubMed Ting JP, Davis BK: CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol. 2005, 23: 387-414. 10.1146/annurev.immunol.23.021704.115616.CrossRefPubMed
26.
go back to reference Krajewska M, Krajewski S, Banares S, Huang X, Turner B, Bubendorf L, Kallioniemi OP, Shabaik A, Vitiello A, Peehl D, et al.: Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res. 2003, 9: 4914-4925.PubMed Krajewska M, Krajewski S, Banares S, Huang X, Turner B, Bubendorf L, Kallioniemi OP, Shabaik A, Vitiello A, Peehl D, et al.: Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res. 2003, 9: 4914-4925.PubMed
27.
go back to reference Mani H, Jaffe ES: Hodgkin lymphoma: an update on its biology with new insights into classification. Clin Lymphoma Myeloma. 2009, 9: 206-216. 10.3816/CLM.2009.n.042.PubMedCentralCrossRefPubMed Mani H, Jaffe ES: Hodgkin lymphoma: an update on its biology with new insights into classification. Clin Lymphoma Myeloma. 2009, 9: 206-216. 10.3816/CLM.2009.n.042.PubMedCentralCrossRefPubMed
28.
go back to reference Diehl V: Hodgkin's disease-from pathology specimen to cure. N Engl J Med. 2007, 357: 1968-1971. 10.1056/NEJMe078173.CrossRefPubMed Diehl V: Hodgkin's disease-from pathology specimen to cure. N Engl J Med. 2007, 357: 1968-1971. 10.1056/NEJMe078173.CrossRefPubMed
29.
go back to reference Kuppers R: Molecular biology of Hodgkin lymphoma. Hematol Am Soc Hematol Educ Program. 2009, 2009: 491-496. 10.1182/asheducation-2009.1.491.CrossRef Kuppers R: Molecular biology of Hodgkin lymphoma. Hematol Am Soc Hematol Educ Program. 2009, 2009: 491-496. 10.1182/asheducation-2009.1.491.CrossRef
30.
go back to reference Berglund M, Enblad G, Thunberg U, Amini RM, Sundstrom C, Roos G, Erlanson M, Rosenquist R, Larsson C, Lagercrantz S: Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma. Mod Pathol. 2007, 20: 63-75. 10.1038/modpathol.3800708.CrossRefPubMed Berglund M, Enblad G, Thunberg U, Amini RM, Sundstrom C, Roos G, Erlanson M, Rosenquist R, Larsson C, Lagercrantz S: Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma. Mod Pathol. 2007, 20: 63-75. 10.1038/modpathol.3800708.CrossRefPubMed
31.
go back to reference Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Bellam N, Byrd JC, Czuczman MS, Fayad LE, Glenn MJ, et al.: Non-Hodgkin's Lymphomas. J Natl Compr Canc Netw. 2011, 9: 484-560.PubMed Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Bellam N, Byrd JC, Czuczman MS, Fayad LE, Glenn MJ, et al.: Non-Hodgkin's Lymphomas. J Natl Compr Canc Netw. 2011, 9: 484-560.PubMed
32.
go back to reference Salaverria I, Siebert R: Follicular lymphoma grade 3B. Best Pract Res Clin Haematol. 2011, 24: 111-119. 10.1016/j.beha.2011.02.002.CrossRefPubMed Salaverria I, Siebert R: Follicular lymphoma grade 3B. Best Pract Res Clin Haematol. 2011, 24: 111-119. 10.1016/j.beha.2011.02.002.CrossRefPubMed
33.
go back to reference Salehi M, Barron M, Merry BJ, Goyns MH: Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing brain. Mech Ageing Dev. 1999, 107: 61-71. 10.1016/S0047-6374(98)00137-7.CrossRefPubMed Salehi M, Barron M, Merry BJ, Goyns MH: Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing brain. Mech Ageing Dev. 1999, 107: 61-71. 10.1016/S0047-6374(98)00137-7.CrossRefPubMed
34.
go back to reference Kabiri Z, Salehi M, Mokarian F, Mohajeri MR, Mahmoodi F, Keyhanian K, Doostan I, Ataollahi MR, Modarressi MH: Evaluation of ARG protein expression in mature B cell lymphomas compared to non-neoplastic reactive lymph node. Cell Immunol. 2009, 259: 111-116. 10.1016/j.cellimm.2009.06.004.CrossRefPubMed Kabiri Z, Salehi M, Mokarian F, Mohajeri MR, Mahmoodi F, Keyhanian K, Doostan I, Ataollahi MR, Modarressi MH: Evaluation of ARG protein expression in mature B cell lymphomas compared to non-neoplastic reactive lymph node. Cell Immunol. 2009, 259: 111-116. 10.1016/j.cellimm.2009.06.004.CrossRefPubMed
Metadata
Title
Apoptosis inhibition or inflammation: the role of NAIP protein expression in Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node
Authors
Safoura Mazrouei
Amin Ziaei
Amir Pouya Tanhaee
Kianoosh Keyhanian
Mahdad Esmaeili
Azar Baradaran
Mansoor Salehi
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2012
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-9-4

Other articles of this Issue 1/2012

Journal of Inflammation 1/2012 Go to the issue