Immunomodulatory role of thymulin in lung diseases

Expert Opinion on Therapeutic Targets

Volumn 14, Issue 2, 2010, Pages 131-141

  Santos, Mário ^a   Henriques Coelho, Tiago ^a   Leite Moreira, Adelino ^a  

^a UNIVERSITY OF PORTO   (Portugal)

Author keywords

Immunomodulator; Inflammation; Lung disease; Thymulin

Indexed keywords

ADENOVIRUS VECTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE P38; THYMULIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AGING; ANTIINFLAMMATORY ACTIVITY; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; GENE THERAPY; HORMONE STRUCTURE; HORMONE SYNTHESIS; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOMODULATION; INFLAMMATION; INFLAMMATORY DISEASE; INTERSTITIAL LUNG DISEASE; LUNG DISEASE; LUNG FIBROSIS; LUNG METASTASIS; NEUROENDOCRINE SYSTEM; NONHUMAN; PROTEIN FUNCTION; PULMONARY HYPERTENSION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; IMMUNOLOGIC FACTORS; INFLAMMATION; LUNG DISEASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; SIGNAL TRANSDUCTION; THYMIC FACTOR, CIRCULATING;

EID: 74949102254     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728220903512991     Document Type: Review

References (95)

1. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008;118(11):3546-3556
2. Savino W, Dardenne M. Neuroendocrine control of thymus physiology. Endocr Rev 2000;21(4):412-443
3. Bach J, Bardenne M, Pleau J, Rosa J. Biochemical characterisation of a serum thymic factor. Nature 1977;266(5597):55-57
4. Laussac JP, Cung MT, Pasdeloup M, et al. NMR study of thymulin, a lymphocyte differentiating thymic nonapeptide. Conformational states of free peptide in solution. J Biol Chem 1986;261(17):7784-7790
5. Gastinel LN, Dardenne M, Pleau JM, Bach JF. Studies on the zinc binding site to the serum thymic factor. Biochim Biophys Acta 1984;797(2):147-155
6. Dardenne M, Pleau JM, Nabarra B, et al. Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci USA 1982;79(17):5370-5373
7. Molinero P, Soutto M, Benot S, et al. Melatonin is responsible for the nocturnal increase observed in serum and thymus of thymosin alpha1 and thymulin concentrations: observations in rats and humans. J Neuroimmunol 2000;103(2):180-188
8. Licastro F, Savorani G, Sarti G, et al. Zinc and thymic hormone-dependent immunity in normal ageing and in patients with senile dementia of the Alzheimer type. J Neuroimmunol 1990;27(2-3):201-208
9. Jambon B, Ziegler O, Maire B, et al. Thymulin (facteur thymique serique) and zinc contents of the thymus glands of malnourished children. Am J Clin Nutr 1988;48(2):335-342
10. Mocchegiani E, Boemi M, Fumelli P, Fabris N. Zinc-dependent low thymic hormone level in type I diabetes. Diabetes 1989;38(7):932-937
11. Mocchegiani E, Fabris N, Travaglini P, et al. Thymic endocrine activity in children with idiopathic growth-hormone deficiency. Int J Neurosci 1991;59(1-3):151-157
12. Consolini R, Legitimo A, Milani M. Primary thymic endocrine failure in HIV-1-infected children. Pathobiology 2000;68(6):251-257
13. Wade S, Bleiberg F, Mosse A, et al. Thymulin (Zn-facteur thymique serique) activity in anorexia nervosa patients. Am J Clin Nutr 1985;42(2):275-280
14. Consolini R, Calleri A, Legitimo A, Massei F. Immunological evaluation of patients with beta-thalassemia major. Acta Haematol 2001;105(1):7-12
15. Farahat SA, Rashed LA, Zawilla NH, Farouk SM. Effect of occupational exposure to elemental mercury in the amalgam on thymulin hormone production among dental staff. Toxicol Ind Health 2009;25(3):159-167
16. Savino W, Dardenne M, Bach JF. Thymic hormone containing cells. III. Evidence for a feed-back regulation of the secretion of the serum thymic factor (FTS) by thymic epithelial cells. Clin Exp Immunol 1983;52(1):7-12
17. Cohen S, Berrih S, Dardenne M, Bach JF. Feedback regulation of the secretion of a thymic hormone (thymulin) by human thymic epithelial cells in culture. Thymus 1986;8(3):109-119
18. Timsit J, Savino W, Safieh B, et al. Growth hormone and insulin-like growth factor-I stimulate hormonal function and proliferation of thymic epithelial cells. J Clin Endocrinol Metab 1992;75(1):183-188
19. Savino W, Wolf B, Aratan-Spire S, Dardenne M. Thymic hormone containing cells. IV. Fluctuations in the thyroid hormone levels in vivo can modulate the secretion of thymulin by the epithelial cells of young mouse thymus. Clin Exp Immunol 1984;55(3):629-635
20. Dardenne M, Savino W, Gagnerault MC, et al. Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells. Endocrinology 1989;125(1):3-12
21. Dardenne M, Savino W, Duval D, et al. Thymic hormone-containing cells. VII. Adrenals and gonads control the in vivo secretion of thymulin and its plasmatic inhibitor. J Immunol 1986;136(4):1303-1308
22. Savino W, Bartoccioni E, Homo-Delarche F, et al. Thymic hormone containing cells-IX. Steroids in vitro modulate thymulin secretion by human and murine thymic epithelial cells. J Steroid Biochem 1988;30(1-6):479-484
23. Folch H, Eller G, Mena M, Esquivel P. Neuroendocrine regulation of thymus hormones: hypothalamic dependence of "facteur thymique serique" level. Cell Immunol 1986;102(1):211-216
24. Goya RG, Gagnerault MC, Sosa YE, Dardenne M. Reduced ability of hypothalamic and pituitary extracts from old mice to stimulate thymulin secretion in vitro. Mech Ageing Dev 1995;83(3):143-154
25. Pleau JM, Fuentes V, Morgat JL, Bach JF. Specific receptors for the serum thymic factor (FTS) in lymphoblastoid cultured cell lines. Proc Natl Acad Sci USA 1980;77(5):2861-2865
26. Gastinel LN, Pleau JM, Dardenne M, et al. High affinity binding sites on plasma membrane obtained from the lymphoblastoid cultured 1301 cell line for highly radioactive serum thymic factor. Biochim Biophys Acta 1982;684(1):117-126
27. Brown OA, Sosa YE, Bolognani F, Goya RG. Thymulin stimulates prolactin and thyrotropin release in an age-related manner. Mech Ageing Dev 1998 104(3):249-262
28. Ben-Efraim S, Keisari Y, Ophir R, et al. Immunopotentiating and immunotherapeutic effects of thymic hormones and factors with special emphasis on thymic humoral factor THF-gamma2. Crit Rev Immunol 1999;19(4):261-284
29. Hadden JW. Thymic endocrinology. Ann NY Acad Sci 1998;840:352-358
30. Reggiani PC, Morel GR, Console GM, et al. The thymus-neuroendocrine axis: physiology, molecular biology, and therapeutic potential of the thymic peptide thymulin. Ann NY Acad Sci 2009;1153:98-106
31. Brown OA, Sosa YE, Dardenne M, et al. Growth hormone-releasing activity of thymulin on pituitary somatotropes is age dependent. Neuroendocrinology 1999;69(1):20-27
32. Daneva T, Spinedi E, Hadid R, Gaillard RC. Impaired hypothalamo- pituitary-adrenal axis function in Swiss nude athymic mice. Neuroendocrinology 1995;62(1):79-86
33. Dardenne M, Saade N, Safieh-Garabedian B. Role of thymulin or its analogue as a new analgesic molecule. Ann NY Acad Sci 2006;1088:153-163
34. Safieh-Garabedian B, Kanaan SA, Jalakhian RH, et al. Hyperalgesia induced by low doses of thymulin injections: possible involvement of prostaglandin E2. J Neuroimmunol 1997;73(1-2):162-168
35. Poole S, Bristow AF, Lorenzetti BB, et al. Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1beta193-195. Br J Pharmacol 1992;106(2):489-492
36. Safieh-Garabedian B, Ochoa-Chaar CI, Poole S, et al. Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection. Neuroscience 2003;121(4):865-873
37. Bach JF, Dardenne M, Pleau JM, Bach MA. Isolation, biochemical characteristics, and biological activity of a circulating thymic hormone in the mouse and in the human. Ann NY Acad Sci 1975;249:186-210
38. Bene MC, Faure G, Bordigoni P, et al. In vitro induction of monoclonal antibody-defined T-cell markers in lymphocytes from immunodeficient children by synthetic serum thymic factor (FTS). Clin Exp Immunol 1982;48(2):423-428
39. Parent G, Chevalier P, Zalles L, et al. In vitro lymphocyte- differentiating effects of thymulin (Zn-FTS) on lymphocyte subpopulations of severely malnourished children. Am J Clin Nutr 1994;60(2):274-278
40. Bardos P, Bach JF. Modulation of mouse natural killer cell activity by the serum thymic factor. Scand J Immunol 1982;16(4):321-325
41. Matsumoto T, Nakano M. Nonspecific stimulation of antibacterial resistance by a synthetic thymic factor (FTS) in mice. Microbiol Immunol 1980;24(12):1185-1197
42. Muzzioli M, Mocchegiani E, Bressani N, et al. In vitro restoration by thymulin of NK activity of cells from old mice. Int J Immunopharmacol 1992;14(1):57-61
43. Haddad JJ, Land SC, Saade NE, Safieh-Garabedian B. Immunomodulatory potential of thymulin-Zn2+ in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway. Biochem Biophys Res Commun 2000;274(2):500-505
44. Kohda Y, Matsunaga Y, Yonogi K, et al. Protective effect of serum thymic factor, FTS, on cephaloridine-induced nephrotoxicity in rats. Biol Pharm Bull 2005;28(11):2087-2091 (Pubitemid 41634256)
45. Kohda Y, Kawai Y, Iwamoto N, et al. Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation. Biochem Pharmacol 2005;70(9):1408-1416
46. Henriques-Coelho T, Oliveira SM, Moura RS, et al. Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway. Endocrinology 2008;149(9):4367-4373
47. Barnes PJ. Novel signal transduction modulators for the treatment of airway diseases. Pharmacol Ther 2006;109(1-2):238-245
48. Barnes PJ, Karin M. Nuclear factor-kB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997;336(15):1066-1071
49. Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kB pathway in the treatment of inflammation and cancer. J Clin Invest 2001;107(2):135-142
50. Wright JG, Christman JW. The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy. Am J Respir Med 2003;2(3):211-219
51. Novoselova EG, Lunin SM, Khrenov MO, et al. Involvement of NF-kB transcription factor in the antiinflammatory activity of thymic peptides. Dokl Biol Sci 2009;428:484-486
52. Haddad JJ. Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced production of proinflammatory cytokines and NF-kB nuclear translocation and activation in the alveolar epithelium: unraveling the molecular immunomodulatory, antiinflammatory effect of thymulin/Zn2+ in vitro. Mol Immunol 2009: published online 21 October 2009, doi: 10.1016/j.molimm.2009. 09.034
53. Qi XF, Kim DH, Yoon YS, et al. The adenylyl cyclase-cAMP system suppresses TARC/CCL17 and MDC/CCL22 production through p38 MAPK and NF-kB in HaCaT keratinocytes. Mol Immunol 2009;46(10):1925-1934
54. Ulivi V, Giannoni P, Gentili C, et al. p38/NF-kB-dependent expression of COX-2 during differentiation and inflammatory response of chondrocytes. J Cell Biochem 2008;104(4):1393-1406
55. Lunin SM, Khrenov MO, Novoselova TV, et al. Thymulin, a thymic peptide, prevents the overproduction of pro-inflammatory cytokines and heat shock protein Hsp70 in inflammation-bearing mice. Immunol Invest 2008;37(8):858-870
56. Safieh-Garabedian B, Dardenne M, Pleau JM, Saade NE. Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat. Br J Pharmacol 2002;136(6):947-955
57. Yamanouchi T, Moromizato H, Kojima S, et al. Prevention of diabetes by thymic hormone in alloxan-treated rats. Eur J Pharmacol 1994;257(1-2):39-46
58. Mizutani M, El-Fotoh M, Mori M, et al. In vivo administration of serum thymic factor (FTS) prevents EMC-D virus-induced diabetes and myocarditis in BALB/cAJcl mice. Arch Virol 1996;141(1):73-83
59. Onodera T, Awaya A. Anti-thyroglobulin antibodies induced with recombinant reovirus infection in BALB/c mice. Immunology 1990;71(4):581-585
60. Kato S, Nakamura H. Suppression of acute experimental allergic encephalomyelitis by synthetic serum thymic factor. Clinical, histopathological, and immunohistochemical studies. Acta Neuropathol 1988;75(4):337-44.
61. Bordigoni P, Faure G, Bene MC, et al. Improvement of cellular immunity and IgA production in immunodeficient children after treatment with synthetic serum thymic factor (FTS). Lancet 1982;2(8293):293-297 (Pubitemid 12089614)
62. Bordigoni P, Bene MC, Faure G, et al. Allogeneic bone marrow transplantation in man: in vitro activity of FTS-Zn on T-cell markers and functions. Br J Haematol 1984;58(4):661-669
63. Safieh-Garabedian B, Ahmed K, Khamashta MA, et al. Thymulin modulates cytokine release by peripheral blood mononuclear cells: a comparison between healthy volunteers and patients with systemic lupus erythematosus. Int Arch Allergy Immunol 1993;101(2):126-131
64. Kim V, Rogers TJ, Criner GJ. New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008;5(4):478-485 (Pubitemid 351669174)
65. Calikoglu M, Sahin G, Unlu A, et al. Leptin and TNF-alpha levels in patients with chronic obstructive pulmonary disease and their relationship to nutritional parameters. Respiration 2004;71(1):45-50
66. Wedzicha JA, Seemungal TA, MacCallum PK, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost 2000;84(2):210-215
67. Yamamoto C, Yoneda T, Yoshikawa M, et al. Airway inflammation in COPD assessed by sputum levels of interleukin-8. Chest 1997;112(2):505-510 (Pubitemid 27349446)
68. Finn PW, Bigby TD. Innate immunity and asthma. Proc Am Thorac Soc 2009;6(3):260-265
69. White ES, Lazar MH, Thannickal VJ. Pathogenetic mechanisms in usual interstitial pneumonia/idiopathic pulmonary fibrosis. J Pathol 2003;201(3):343-354
70. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 2008;118(7):2372-2379.
71. Hagen M, Fagan K, Steudel W, et al. Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol 2007;292(6):L1473-9
72. Michelakis ED, Wilkins MR, Rabinovitch M. Emerging concepts and translational priorities in pulmonary arterial hypertension. Circulation 2008;118(14):1486-1495
73. Daley E, Emson C, Guignabert C, et al. Pulmonary arterial remodeling induced by a Th2 immune response. J Exp Med 2008;205(2):361-372
74. Phan SH, Kunkel SL. Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp Lung Res 1992;18(1):29-43
75. Yara S, Kawakami K, Kudeken N, et al. FTS reduces bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice. Clin Exp Immunol 2001;124(1):77-85.
76. Kramer BW, Moss TJ, Willet KE, et al. Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med 2001;164(6):982-988
77. Kramer BW, Kramer S, Ikegami M, Jobe AH. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2002;283(2):L452-9 (Pubitemid 34804003)
78. Land SC, Darakhshan F. Thymulin evokes IL-6-C/EBPbeta regenerative repair and TNF-alpha silencing during endotoxin exposure in fetal lung explants. Am J Physiol Lung Cell Mol Physiol 2004;286(3):L473-87
79. Tomazic VJ, Sacasa CR, Loftus A, et al. Thymic factor-induced reduction of pulmonary metastases in mice with FSA-1 fibrosarcoma. Clin Exp Metastasis 1988;6(1):17-25
80. Goya RG, Gagnerault MC, De Moraes MC, et al. In vivo effects of growth hormone on thymus function in aging mice. Brain Behav Immun 1992;6(4):341-354
81. Incefy GS, Pahwa S, Pahwa R, et al. Low circulating thymulin-like activity in children with AIDS and AIDS-related complex. AIDS Res 1986 Spring;2(2):109-116
82. Incefy GS, Dardenne M, Pahwa S, et al. Thymic activity in severe combined immunodeficiency diseases. Proc Natl Acad Sci USA 1977;74(3):1250-1253
83. Iwata T, Incefy GS, Cunningham-Rundles S, et al. Circulating thymic hormone activity in patients with primary and secondary immunodeficiency diseases. Am J Med 1981;71(3):385-394
84. Goya RG, Reggiani PC, Vesenbeckh SM, et al. Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice. Am J Physiol Endocrinol Metab 2007;293(1):E182-7
85. Garcia de Bravo MM, Polo MP, Reggiani PC, et al. Partial prevention of hepatic lipid alterations in nude mice by neonatal thymulin gene therapy. Lipids 2006;41(8):753-757
86. Stone D, Xiong W, Williams JC, et al. Adenovirus expression of IL-1 and NF-kB inhibitors does not inhibit acute adenoviral-induced brain inflammation, but delays immune system-mediated elimination of transgene expression. Mol Ther 2003;8(3):400-411
87. Reggiani PC, Herenu CB, Rimoldi OJ, et al. Gene therapy for long-term restoration of circulating thymulin in thymectomized mice and rats. Gene Ther 2006;13(16):1214-1221.
88. Morel GR, Brown OA, Reggiani PC, et al. Peripheral and mesencephalic transfer of a synthetic gene for the thymic peptide thymulin. Brain Res Bull 2006;69(6):647-651
89. Calenda A, Cordonnier A, Lederer F, et al. Production of biologically active thymulin in Esherichia coli through expression of a chemically synthesized gene. Biotechnol Lett 1998;10:155-160
90. Kolb M, Martin G, Medina M, et al. Gene therapy for pulmonary diseases. Chest 2006;130(3):879-884
91. Henriques-Coelho T, Gonzaga S, Endo M, et al. Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection. Mol Ther 2007;15(2):340-347
92. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet 2009;373(9678):1905-1917
93. Adcock IM, Barnes PJ. Molecular mechanisms of corticosteroid resistance. Chest 2008;134(2):394-401
94. Irusen E, Matthews JG, Takahashi A, et al. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol 2002;109(4):649-657.
95. Szatmary Z, Garabedian MJ, Vilcek J. Inhibition of glucocorticoid receptor-mediated transcriptional activation by p38 mitogen-activated protein (MAP) kinase. J Biol Chem 2004;279(42):43708-43715