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Respiratory Research
Published in: Respiratory Research 1/2013

Open Access 01-12-2013 | Research

Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice

Authors: Wei Liu, Jing Wan, Jian-Zhong Han, Chen Li, Dan-Dan Feng, Shao-Jie Yue, Yan-Hong Huang, Yi Chen, Qing-Mei Cheng, Yang Li, Zi-Qiang Luo

Published in: Respiratory Research | Issue 1/2013

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Abstract

Background

Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions. In the present study, we investigated whether AF-1 has a protective effect against bleomycin-induced pulmonary fibrosis.

Methods

C57BL/6 mice were injected with bleomycin intratracheally to create an animal model of bleomycin-induced pulmonary fibrosis. On Day 7 and Day 28, we examined the anti-inflammatory effect and antifibrotic effect, respectively, of AF-1 on the bleomycin-treated mice. The effects of AF-1 on the transforming growth factor-beta 1 (TGF-β1)-induced proliferation of murine lung fibroblasts (NIH3T3) were examined by a bromodeoxycytidine (BrdU) incorporation assay and cell cycle analysis.

Results

Severe lung inflammation and fibrosis were observed in the bleomycin-treated mice on Day 7 and Day 28, respectively. Administration of AF-1 significantly reduced the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the lung homogenates on Day 7. Histological examination revealed that AF-1 markedly reduced the number of infiltrating cells on Day 7 and attenuated the collagen deposition and destruction of lung architecture on Day 28. The hydroxyproline (HYP) content was significantly decreased in the AF-1-treated mice. In vitro, AF-1 inhibited the TGF-β1-induced proliferation of NIH3T3 cells, which was mediated by the UG receptor.

Conclusions

AF-1 has anti-inflammatory and antifibrotic actions in bleomycin-induced lung injury. We propose that the antifibrotic effect of AF-1 might be related to its suppression of fibroblast growth in bleomycin-treated lungs and that AF-1 has potential as a new therapeutic tool for pulmonary fibrosis.
Appendix
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Literature
1.
O’Connell OJ, Kennedy MP, Henry MT: Idiopathic pulmonary fibrosis: treatment update. Adv Ther. 2011, 28: 986-99. 10.1007/s12325-011-0066-5.PubMedCrossRef
2.
Mukherjee AB, Zhang Z, Chilton BS: Uteroglobin: a steroid-inducible immunomodulatory protein that founded the Secretoglobin superfamily. Endocr Rev. 2007, 28: 707-25. 10.1210/er.2007-0018.PubMedCrossRef
3.
Wang H, Long XB, Cao PP, Wang N, Liu Y, Cui YH, Huang SK, Liu Z: Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis. Am J Respir Crit Care Med. 2010, 181: 908-16. 10.1164/rccm.200904-0597OC.PubMedPubMedCentralCrossRef
4.
Szabo E, Goheer A, Witschi H, Linnoila RI: Overexpression of CC10 modifies neoplastic potential in lung cancer cells. Cell Growth Differ. 1998, 9: 475-85.PubMed
5.
Zhang Z, Kundu GC, Panda D, Mandal AK, Mantile-Selvaggi G, Peri A, Yuan CJ, Mukherjee AB: Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene. Proc Natl Acad Sci U S A. 1999, 96: 3963-8. 10.1073/pnas.96.7.3963.PubMedPubMedCentralCrossRef
6.
Yang SH, Shin SJ, Oh JE, Jin JZ, Chung NH, Lim CS, Kim S, Kim YS: The protective role of uteroglobin through the modulation of tissue transglutaminase in the experimental crescentic glomerulonephritis. Nephrol Dial Transplant. 2008, 23: 3437-45. 10.1093/ndt/gfn268.PubMedCrossRef
7.
Li C, Hu W, Han J, Shen L, Yue S, Feng D, Luo Z: Clara cells ablation increases Ki67 immunoexpression and histological grade in bleomycin lung [abstract]. Regul Peptides. 2006, 135: 141-141.
8.
Lee YC, Zhang Z, Mukherjee AB: Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis. FEBS Lett. 2006, 580: 4515-20. 10.1016/j.febslet.2006.07.031.PubMedCrossRef
9.
Miele L, Cordella-Miele E, Facchiano A, Mukherjee AB: Novel anti-inflammatory peptides from the region of highest similarity between uteroglobin and lipocortin I. Nature. 1988, 335: 726-30. 10.1038/335726a0.PubMedCrossRef
10.
Miele L: Antiflammins. Bioactive peptides derived from uteroglobin. Ann N Y Acad Sci. 2000, 923: 128-40.PubMedCrossRef
11.
Zouki C, Ouellet S, Filep JG: The anti-inflammatory peptides, antiflammins, regulate the expression of adhesion molecules on human leukocytes and prevent neutrophil adhesion to endothelial cells. FASEB J. 2000, 14: 572-80.PubMed
12.
Han J, Li C, Liu H, Fen D, Hu W, Liu Y, Guan C, Luo ZQ: Inhibition of lipopolysaccharide-mediated rat alveolar macrophage activation in vitro by antiflammin-1. Cell Biol Int. 2008, 32: 1108-15. 10.1016/j.cellbi.2008.04.023.PubMedCrossRef
13.
Lloret S, Moreno JJ: Effect of nonapeptide fragments of uteroglobin and lipocortin I on oedema and mast cell degranulation. Eur J Pharmacol. 1994, 264: 379-84. 10.1016/0014-2999(94)00500-1.PubMedCrossRef
14.
Gao J, Zhao J, Rayner SE, Van Helden DF: Evidence that the ATP-induced increase in vasomotion of guinea-pig mesenteric lymphatics involves an endothelium-dependent release of thromboxane A2. Br J Pharmacol. 1999, 127: 1597-602. 10.1038/sj.bjp.0702710.PubMedPubMedCentralCrossRef
15.
Vostal JG, Mukherjee AB, Miele L, Shulman NR: Novel peptides derived from a region of local homology between uteroglobin and lipocortin-1 inhibit platelet aggregation and secretion. Biochem Biophys Res Commun. 1989, 165: 27-36. 10.1016/0006-291X(89)91029-2.PubMedCrossRef
16.
Chan CC, Ni M, Miele L, Cordella-Miele E, Ferrick M, Mukherjee AB, Nussenblatt RB: Effects of antiflammins on endotoxin-induced uveitis in rats. Arch Ophthalmol. 1991, 109: 278-81. 10.1001/archopht.1991.01080020124058.PubMedCrossRef
17.
Lloret S, Moreno JJ: In vitro and in vivo effects of the anti-inflammatory peptides, antiflammins. Biochem Pharmacol. 1992, 44: 1437-41. 10.1016/0006-2952(92)90546-U.PubMedCrossRef
18.
Mize NK, Buttery M, Ruis N, Leung I, Cormier M, Daddona P: Antiflammin 1 peptide delivered non-invasively by iontophoresis reduces irritant-induced inflammation in vivo. Exp Dermatol. 1997, 6: 181-5. 10.1111/j.1600-0625.1997.tb00203.x.PubMedCrossRef
19.
Merrifield RB: Solid phase peptide synthesis. I: the synthesis of a tetrapeptide. J Am Chem Soc. 1963, 85: 2149-54. 10.1021/ja00897a025.CrossRef
20.
Ashcroft T, Simpson JM, Timbrell V: Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988, 41: 467-70. 10.1136/jcp.41.4.467.PubMedPubMedCentralCrossRef
21.
Chaudhary NI, Schnapp A, Park JE: Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. Am J Respir Crit Care Med. 2006, 173: 769-76. 10.1164/rccm.200505-717OC.PubMedCrossRef
22.
Li C, Han J, Li L, Yue S, Li J, Feng D, Liu H, Jiang D, Qin X, Luo Z: Interaction of antiflammin-1 with uteroglobin-binding protein induces phosphorylation of ERK1/2 in NIH 3T3 cells. Peptides. 2007, 28: 2137-45. 10.1016/j.peptides.2007.08.027.PubMedCrossRef
23.
Mouratis MA, Aidinis V: Modeling pulmonary fibrosis with bleomycin. Curr Opin Pulm Med. 2011, 17: 355-61. 10.1097/MCP.0b013e328349ac2b.PubMedCrossRef
24.
Imazu Y, Yanagi S, Miyoshi K, Tsubouchi H, Yamashita S, Matsumoto N, Ashitani J, Kangawa K, Nakazato M: Ghrelin ameliorates bleomycin-induced acute lung injury by protecting alveolar epithelial cells and suppressing lung inflammation. Eur J Pharmacol. 2011, 672: 153-8. 10.1016/j.ejphar.2011.09.183.PubMedCrossRef
25.
Yang HZ, Wang JP, Mi S, Liu HZ, Cui B, Yan HM, Yan J, Li Z, Liu H, Hua F, Lu W, Hu ZW: TLR4 activity is required in the resolution of pulmonary inflammation and fibrosis after acute and chronic lung injury. Am J Pathol. 2012, 180: 275-92. 10.1016/j.ajpath.2011.09.019.PubMedCrossRef
26.
Moeller A, Ask K, Warburton D, Gauldie J, Kolb M: The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis?. Int J Biochem Cell Biol. 2008, 40: 362-82. 10.1016/j.biocel.2007.08.011.PubMedPubMedCentralCrossRef
27.
Fernandez IE, Eickelberg O: The impact of TGF-β on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc. 2012, 9: 111-6. 10.1513/pats.201203-023AW.PubMedCrossRef
28.
Stacey DW, Hitomi M: Cell cycle studies based upon quantitative image analysis. Cytometry A. 2008, 73: 270-8.PubMedCrossRef
29.
Biggar KK, Storey KB: Evidence for cell cycle suppression and microRNA regulation of cyclin D1 during anoxia exposure in turtles. Cell Cycle. 2012, 11: 1705-13. 10.4161/cc.19790.PubMedCrossRef
30.
De Vita F, Riccardi M, Malanga D, Scrima M, De Marco C, Viglietto G: PKC-dependent phosphorylation of p27 at T198 contributes to p27 stabilization and cell cycle arrest. Cell Cycle. 2012, 11: 1583-92. 10.4161/cc.20003.PubMedCrossRef
31.
Kundu GC, Mantile G, Miele L, Cordella-Miele E, Mukherjee AB: Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site. Proc Natl Acad Sci U S A. 1996, 93: 2915-9. 10.1073/pnas.93.7.2915.PubMedPubMedCentralCrossRef
32.
Kundu GC, Mandal AK, Zhang Z, Mantile-Selvaggi G, Mukherjee AB: Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. J Biol Chem. 1998, 273: 22819-24. 10.1074/jbc.273.35.22819.PubMedCrossRef
33.
Kundu GC, Zhang Z, Mantile-Selvaggi G, Mandal A, Yuan CJ, Mukherjee AB: Uteroglobin binding proteins: regulation of cellular motility and invasion in normal and cancer cells. Ann N Y Acad Sci. 2000, 923: 234-48.PubMedCrossRef
34.
Wojnar P, Lechner M, Merschak P, Redl B: Molecular cloning of a novel lipocalin-1 interacting human cell membrane receptor using phage display. J Biol Chem. 2001, 276: 20206-12. 10.1074/jbc.M101762200.PubMedCrossRef
35.
Zhang Z, Kim SJ, Chowdhury B, Wang J, Lee YC, Tsai PC, Choi M, Mukherjee AB: Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion. Gene. 2006, 369: 66-71.PubMedCrossRef
36.
Moreno JJ: Effects of antiflammins on transglutaminase and phospholipase A2 activation by transglutaminase. Int Immunopharmacol. 2006, 6: 300-3. 10.1016/j.intimp.2005.08.001.PubMedCrossRef
37.
Olsen KC, Sapinoro RE, Kottmann RM, Kulkarni AA, Iismaa SE, Johnson GV, Thatcher TH, Phipps RP, Sime PJ: Transglutaminase 2 and its role in pulmonary fibrosis. Am J Respir Crit Care Med. 2011, 184: 699-707. 10.1164/rccm.201101-0013OC.PubMedPubMedCentralCrossRef
38.
Oh K, Park HB, Byoun OJ, Shin DM, Jeong EM, Kim YW, Kim YS, Melino G, Kim IG, Lee DS: Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice. J Exp Med. 2011, 208: 1707-19. 10.1084/jem.20101457.PubMedPubMedCentralCrossRef
Metadata
Title
Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice
Authors
Wei Liu
Jing Wan
Jian-Zhong Han
Chen Li
Dan-Dan Feng
Shao-Jie Yue
Yan-Hong Huang
Yi Chen
Qing-Mei Cheng
Yang Li
Zi-Qiang Luo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2013
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-14-101

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