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Published in: Respiratory Research 1/2011

Open Access 01-12-2011 | Research

β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up

Authors: Maria De Santis, Rosanna Inzitari, Silvia L Bosello, Giusy Peluso, Chiara Fanali, Federica Iavarone, Gaetano Zizzo, Mario Bocci, Tiziana Cabras, Irene Messana, Leo Fuso, Francesco Varone, Gabriella Pagliari, Massimo Castagnola, Gianfranco Ferraccioli

Published in: Respiratory Research | Issue 1/2011

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Abstract

Background

β-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters.

Methods

β-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls.

Results

Thymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis.

Conclusions

We describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.
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Literature
2.
go back to reference Huff T, Muller CS, Otto AM, Natzker R, Hannappel E: beta-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001, 33: 205-220. 10.1016/S1357-2725(00)00087-X.CrossRefPubMed Huff T, Muller CS, Otto AM, Natzker R, Hannappel E: beta-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001, 33: 205-220. 10.1016/S1357-2725(00)00087-X.CrossRefPubMed
3.
go back to reference Santelli G, Califano D, Chiappetta G, Vento MT, Bartoli PC, Zullo F, Trapasso F, Viglietto G, Fusco A: Thymosin beta-10 gene overexpression is a general event in human carcinogenesis. Am J Pathol. 1999, 155: 799-804. 10.1016/S0002-9440(10)65178-4.CrossRefPubMedPubMedCentral Santelli G, Califano D, Chiappetta G, Vento MT, Bartoli PC, Zullo F, Trapasso F, Viglietto G, Fusco A: Thymosin beta-10 gene overexpression is a general event in human carcinogenesis. Am J Pathol. 1999, 155: 799-804. 10.1016/S0002-9440(10)65178-4.CrossRefPubMedPubMedCentral
4.
go back to reference Capelli E, Campo I, Panelli S, Damiani G, Barbone MG, Lucchelli A, Cuccia M: Evaluation of gene expression in human lymphocytes activated in the presence of melatonin. Int Immunopharmacol. 2002, 2 (7): 885-92. 10.1016/S1567-5769(02)00021-8.CrossRefPubMed Capelli E, Campo I, Panelli S, Damiani G, Barbone MG, Lucchelli A, Cuccia M: Evaluation of gene expression in human lymphocytes activated in the presence of melatonin. Int Immunopharmacol. 2002, 2 (7): 885-92. 10.1016/S1567-5769(02)00021-8.CrossRefPubMed
5.
go back to reference Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, Fiorita A, Paludetti G, Manni A, Nemolato S, Faa G, Castagnola M, Messana I: HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci. 2009, 32 (1): 57-63. 10.1002/jssc.200800496.CrossRefPubMed Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, Fiorita A, Paludetti G, Manni A, Nemolato S, Faa G, Castagnola M, Messana I: HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci. 2009, 32 (1): 57-63. 10.1002/jssc.200800496.CrossRefPubMed
6.
go back to reference Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK: Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999, 113 (3): 364-8. 10.1046/j.1523-1747.1999.00708.x.CrossRefPubMed Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK: Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999, 113 (3): 364-8. 10.1046/j.1523-1747.1999.00708.x.CrossRefPubMed
7.
go back to reference Smart N, Rossdeutsch A, Riley PR: Thymosin b4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007, 10: 229-241. 10.1007/s10456-007-9077-x.CrossRefPubMed Smart N, Rossdeutsch A, Riley PR: Thymosin b4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007, 10: 229-241. 10.1007/s10456-007-9077-x.CrossRefPubMed
8.
go back to reference Zhang T, Li X, Yu W, Yan Z, Zou H, He X: Overexpression of thymosin beta-10 inhibits VEGF mRNA expression, autocrine VEGF protein production, and tube formation in hypoxia-induced monkey choroid-retinal endothelial cells. Ophthalmic Res. 2009, 41 (1): 36-43. 10.1159/000163220.CrossRefPubMed Zhang T, Li X, Yu W, Yan Z, Zou H, He X: Overexpression of thymosin beta-10 inhibits VEGF mRNA expression, autocrine VEGF protein production, and tube formation in hypoxia-induced monkey choroid-retinal endothelial cells. Ophthalmic Res. 2009, 41 (1): 36-43. 10.1159/000163220.CrossRefPubMed
9.
go back to reference Barnaeva E, Nadezhda A, Hannappel E, Sjogren MH, Rojkind M: Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells. Ann NY Acad Sci. 2007, 1112: 154-60. 10.1196/annals.1415.035.CrossRefPubMed Barnaeva E, Nadezhda A, Hannappel E, Sjogren MH, Rojkind M: Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells. Ann NY Acad Sci. 2007, 1112: 154-60. 10.1196/annals.1415.035.CrossRefPubMed
10.
go back to reference Sosne G, Qiu P, Christopherson PL, Wheater MK: Thymosin b4 suppression of corneal NFkB: a potential anti-infllammatory pathway. Exp Eye Res. 2007, 84: 663-669. 10.1016/j.exer.2006.12.004.CrossRefPubMedPubMedCentral Sosne G, Qiu P, Christopherson PL, Wheater MK: Thymosin b4 suppression of corneal NFkB: a potential anti-infllammatory pathway. Exp Eye Res. 2007, 84: 663-669. 10.1016/j.exer.2006.12.004.CrossRefPubMedPubMedCentral
11.
go back to reference Young JD, Lawrence AJ, MacLean AG, Leung BP, McInnes IB, Canas B, Pappin DJ, Stevenson RD: Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med. 1999, 5 (12): 1424-7. 10.1038/71002.CrossRefPubMed Young JD, Lawrence AJ, MacLean AG, Leung BP, McInnes IB, Canas B, Pappin DJ, Stevenson RD: Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med. 1999, 5 (12): 1424-7. 10.1038/71002.CrossRefPubMed
12.
go back to reference Badamchian M, Damavandy AA, Damavandy H, Wadhwa SD, Katz B, Goldstein AL: Identification and quantification of thymosin β4 in human saliva and tears. Ann NY Acad Sci. 2007, 1112: 458-465. 10.1196/annals.1415.046.CrossRefPubMed Badamchian M, Damavandy AA, Damavandy H, Wadhwa SD, Katz B, Goldstein AL: Identification and quantification of thymosin β4 in human saliva and tears. Ann NY Acad Sci. 2007, 1112: 458-465. 10.1196/annals.1415.046.CrossRefPubMed
13.
go back to reference Subcommittee for scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 23: 581-90. 10.1002/art.1780230510.CrossRef Subcommittee for scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 23: 581-90. 10.1002/art.1780230510.CrossRef
14.
go back to reference LeRoy EC, Black C, Fleishmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wolheim F: Scleroderma (systemic sclerosis): classification, subset and pathogenesis. J Rheumatol. 1988, 15: 202-5.PubMed LeRoy EC, Black C, Fleishmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wolheim F: Scleroderma (systemic sclerosis): classification, subset and pathogenesis. J Rheumatol. 1988, 15: 202-5.PubMed
15.
go back to reference De Santis M, Bosello S, La Torre G, Capuano A, Tolusso B, Pagliari G, Pistelli R, Danza FM, Zoli A, Ferraccioli G: Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis. Respir Res. 2005, 17: 6-96 De Santis M, Bosello S, La Torre G, Capuano A, Tolusso B, Pagliari G, Pistelli R, Danza FM, Zoli A, Ferraccioli G: Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis. Respir Res. 2005, 17: 6-96
16.
go back to reference American Thoracic Society: Standardization of Spirometry-1994 Update. Am J Respir Crit Care Med. 1995, 152: 1107-1136.CrossRef American Thoracic Society: Standardization of Spirometry-1994 Update. Am J Respir Crit Care Med. 1995, 152: 1107-1136.CrossRef
17.
go back to reference American Thoracic Society: Single breath Carbon Monoxide Diffusing Capacity (Transfer Factor). Recommendation for a standard technique-1995 Update. Am J Respir Crit Care Med. 1995, 152: 2185-2198.CrossRef American Thoracic Society: Single breath Carbon Monoxide Diffusing Capacity (Transfer Factor). Recommendation for a standard technique-1995 Update. Am J Respir Crit Care Med. 1995, 152: 2185-2198.CrossRef
18.
go back to reference Egan JJ, Martinez FJ, Wells AU, Williams T: Lung function estimates in idiopathic pulmonary fibrosis: the potential for a simple classification. Thorax. 2005, 60: 270-273. 10.1136/thx.2004.035436.CrossRefPubMedPubMedCentral Egan JJ, Martinez FJ, Wells AU, Williams T: Lung function estimates in idiopathic pulmonary fibrosis: the potential for a simple classification. Thorax. 2005, 60: 270-273. 10.1136/thx.2004.035436.CrossRefPubMedPubMedCentral
19.
go back to reference Behr J, Furst DE: Pulmonary function tests. Rheumatol. 2008, 47: 65-67. 10.1093/rheumatology/ken313.CrossRef Behr J, Furst DE: Pulmonary function tests. Rheumatol. 2008, 47: 65-67. 10.1093/rheumatology/ken313.CrossRef
20.
go back to reference Medsger TA, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W: Assessment of disease severity and prognosis in Scleroderma. Clin Exp Rheumatol. 2003, 29: 42-46. Medsger TA, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W: Assessment of disease severity and prognosis in Scleroderma. Clin Exp Rheumatol. 2003, 29: 42-46.
21.
go back to reference Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Scleroderma Lung Study Research Group: Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006, 354 (25): 2655-66. 10.1056/NEJMoa055120.CrossRefPubMed Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Scleroderma Lung Study Research Group: Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006, 354 (25): 2655-66. 10.1056/NEJMoa055120.CrossRefPubMed
22.
go back to reference Hannappel E, van Kampen M: Determination of thymosin beta 4 in human blood cells and serum. J Chromatogr. 1987, 26: 397-279-285 Hannappel E, van Kampen M: Determination of thymosin beta 4 in human blood cells and serum. J Chromatogr. 1987, 26: 397-279-285
23.
go back to reference Mannherz HG, Hannappel E: The β-Thymosins: intracellular and extracellular activities of a versatile actin binding protein family. Cell Motil Cytoskeleton. 2009, 66: 839-851. 10.1002/cm.20371.CrossRefPubMed Mannherz HG, Hannappel E: The β-Thymosins: intracellular and extracellular activities of a versatile actin binding protein family. Cell Motil Cytoskeleton. 2009, 66: 839-851. 10.1002/cm.20371.CrossRefPubMed
24.
go back to reference Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D: Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004, 432: 466-72. 10.1038/nature03000.CrossRefPubMed Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D: Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004, 432: 466-72. 10.1038/nature03000.CrossRefPubMed
25.
go back to reference Sosne G, Christopherson PL, Barrett RP, Fridman R: Thymosin b4 modulates corneal matrix metalloproteinase levels and polymorphonuclear cell infiltration after alkali injury. Invest Ophthalmol Vis Sci. 2005, 46: 2388-2395. 10.1167/iovs.04-1368.CrossRefPubMed Sosne G, Christopherson PL, Barrett RP, Fridman R: Thymosin b4 modulates corneal matrix metalloproteinase levels and polymorphonuclear cell infiltration after alkali injury. Invest Ophthalmol Vis Sci. 2005, 46: 2388-2395. 10.1167/iovs.04-1368.CrossRefPubMed
26.
go back to reference Zheng X, Wu S, Hincapie M, Hancock WS: Study of the human plasma proteome of rheumatoid arthritis. J Chromatogr A. 2009, 1216: 3538-3545. 10.1016/j.chroma.2009.01.063.CrossRefPubMed Zheng X, Wu S, Hincapie M, Hancock WS: Study of the human plasma proteome of rheumatoid arthritis. J Chromatogr A. 2009, 1216: 3538-3545. 10.1016/j.chroma.2009.01.063.CrossRefPubMed
27.
go back to reference Taggart C, Cervantes-Laurean D, Kim G, McElvaney NG, Wehr N, Moss J, Levine RL: Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity. J Biol Chem. 2000, 275 (35): 27258-27265.PubMed Taggart C, Cervantes-Laurean D, Kim G, McElvaney NG, Wehr N, Moss J, Levine RL: Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity. J Biol Chem. 2000, 275 (35): 27258-27265.PubMed
28.
go back to reference Kowal-Bielecka O, Kowal K, Highland KB, Silver RM: Bronchoalveolar Lavage Fluid in Scleroderma Interstitial Lung Disease: Technical Aspects and Clinical Correlations. Sem Arthritis Rheum. 2009, 40 (1): 73-88. 10.1016/j.semarthrit.2008.10.009.CrossRef Kowal-Bielecka O, Kowal K, Highland KB, Silver RM: Bronchoalveolar Lavage Fluid in Scleroderma Interstitial Lung Disease: Technical Aspects and Clinical Correlations. Sem Arthritis Rheum. 2009, 40 (1): 73-88. 10.1016/j.semarthrit.2008.10.009.CrossRef
29.
go back to reference Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, Alms WJ, White B: Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999, 42 (6): 1168-78. 10.1002/1529-0131(199906)42:6<1168::AID-ANR13>3.0.CO;2-L.CrossRefPubMed Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, Alms WJ, White B: Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999, 42 (6): 1168-78. 10.1002/1529-0131(199906)42:6<1168::AID-ANR13>3.0.CO;2-L.CrossRefPubMed
30.
go back to reference Vasakova M, Sterclova M, Kolesar L, Slavcev A, Pohunek P, Sulc J, Skibova J, Striz I: Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases. Scand J Immunol. 2009, 69 (3): 268-74. 10.1111/j.1365-3083.2008.02222.x.CrossRefPubMed Vasakova M, Sterclova M, Kolesar L, Slavcev A, Pohunek P, Sulc J, Skibova J, Striz I: Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases. Scand J Immunol. 2009, 69 (3): 268-74. 10.1111/j.1365-3083.2008.02222.x.CrossRefPubMed
Metadata
Title
β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up
Authors
Maria De Santis
Rosanna Inzitari
Silvia L Bosello
Giusy Peluso
Chiara Fanali
Federica Iavarone
Gaetano Zizzo
Mario Bocci
Tiziana Cabras
Irene Messana
Leo Fuso
Francesco Varone
Gabriella Pagliari
Massimo Castagnola
Gianfranco Ferraccioli
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2011
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-12-22

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