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Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells

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Abstract

The morphology of human fetal liver cells treated with both oncostatin M and dexamethasone was strikingly different from those of cells treated with either oncostatin M or dexamethasone alone. Cotreatment with oncostatin M and dexamethasone resulted in the appearance of numerous large vacuoles. The size of the vacuoles varied among individual cells, ranging from 0.05 to 20 μm depending on the cell. Electron microscopy indicated that swollen large vacuoles in the human fetal liver cells were generally electron lucent. On the other hand, relatively small vacuoles about 2 μm in diameter were discrete structures that contained electron-dense material, such as partially degraded cytoplasmic membrane, cytoplasm, or organelle components. An autophagosome-like organelle was formed in cytoplasm. Electron microscopic analysis indicated direct fusion among the vacuoles formed in the cytoplasm of human fetal liver cells. To our knowledge, this is the first report of large swollen vacuoles formed in cells by the cooperative effects of oncostatin M and dexamethasone.

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References

  1. Gomez-Lechon MJ (1999) Oncostatin M. Signal transduction and biological activity. Life Sci 65:2019–2030

    Article  PubMed  CAS  Google Scholar 

  2. Tanaka M, Miyajima A (2003) Oncostatin M, a multifunctional cytokine. Rev Physiol Biochem Pharmacol 149:39–52

    Article  PubMed  CAS  Google Scholar 

  3. Miyajima A, Kinoshita T, Tanaka M, Kamiya A, Mukouyama Y, Hara T (2000) Role of oncostatin M in hematopoiesis and liver development. Cytokine Growth Factor Rev 11:177–183

    Article  PubMed  CAS  Google Scholar 

  4. Kamiya A, Kinoshita T, Ito Y, Matsui T, Morikawa Y, Senba E, Nakashima, K, Taga T, Yoshida K, Kishimoto T, Miyajima A (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J 18: 2127–2136

    Article  PubMed  CAS  Google Scholar 

  5. Kinoshita T, Sekiguchi T, Xu MJ, Ito Y, Kamiya A, Tsuji K, Nakahata T, Miyajima A (1999) Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis. Proc Natl Acad Sci U S A 96:7265–7270

    Article  PubMed  CAS  Google Scholar 

  6. La’zaro CA, Croager EJ, Mitchell C, Campbell JS, Yu C, Foraker J, Rhim JA, Yeoh GC, Fausto N (2003) Establishment, characterization, and long-term maintenance of cultures of human fetal hepatocytes. Hepatology 38:1095–1106

    Article  Google Scholar 

  7. Andrade MVM, Hiragun T, Beaven MA (2004) Dexamethasone suppresses antigen-induced activation of phosphatidylinositol 3-kinase and downstream responses in mast cells. J Immunol 172: 7254–7262

    PubMed  CAS  Google Scholar 

  8. Johnson EE, Overmeyer JH, Gunning WT, Maltese WA (2006) Gene silencing reveals a specific function of hVps34 phosphatidylinositol 3-kinase in late versus early endosomes. J Cell Sci 119:1219–1232

    Article  PubMed  CAS  Google Scholar 

  9. Reaves BJ, Bright NA, Mullock BM, Luzio JP (1996) The effect of wortmannin on the localisation of lysosomal type I integral membrane glycoproteins suggests a role for phosphoinositide 3-kinase activity in regulating membrane traffic late in the endocytic pathway. J Cell Sci 109:749–762

    PubMed  CAS  Google Scholar 

  10. Smyth DC, Kerr C, Richards CD (2006) Oncostatin M-induced IL-6 expression in murine fibroblasts requires the activation of protein kinase Cδ. J Immunol 177:8740–8747

    PubMed  CAS  Google Scholar 

  11. Telford JL, Ghiara P, Dell’Orco M, Comanducci M, Burroni D, Bugnoli M, Tecce MF, Censini S, Covacci A, Xiang Z, Papini E, Montecucco C, Parente L, Rappuoli R (1994) Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J Exp Med 179:1653–1658

    Article  PubMed  CAS  Google Scholar 

  12. Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270: 17771–17777

    Article  PubMed  CAS  Google Scholar 

  13. Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simoes M (2002) Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94:1680–1687

    PubMed  CAS  Google Scholar 

  14. Fujikawa A, Shirasaka D, Yamamoto S, Ota H, Yahiro K, Fukada M, Shintani T, Wada A, Aoyama N, Hirayama T, Fukamachi H (2003) Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori. Nat Genet 33:375–381

    Article  PubMed  CAS  Google Scholar 

  15. Papini E, Zoratti M, Cover TL (2001) In search of the Helicobacter pylori VacA mechanism of action. Toxicon 39:1757–1767

    Article  PubMed  CAS  Google Scholar 

  16. Montecucco C, de Bernard M (2003) Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Microbes Infect 5:715–721

    Article  PubMed  CAS  Google Scholar 

  17. Kuronita T, Eskelinen EL, Fujita H, Saftig P, Himeno M, Tanaka Y (2002) A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology. J Cell Sci 115:4117–4131

    Article  PubMed  CAS  Google Scholar 

  18. Eskelinen EL, Schmidt CK, Neu S, Willenborg M, Fuertes G, Salvador N, Tanaka Y, Lullmann-Rauch R, Hartmann D, Heeren J, von Figura K, Knecht E, Saftig P (2004) Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell 15:3132–3145

    Article  PubMed  CAS  Google Scholar 

  19. Kaul A, Overmeyer JH, Maltese WA (2007) Activated Ras induces cytoplasmic vacuolation and non-apoptotic death in glioblastoma cells via novel effector pathways. Cell Signal 19:1034–1043

    Article  PubMed  CAS  Google Scholar 

  20. Ohkuma S, Poole B (1981) Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances. J Cell Biol 90:656–664

    Article  PubMed  CAS  Google Scholar 

  21. Maruyama M, Matsunaga T, Harada E, Ohmori S (2007) Comparison of basal gene expression and induction of CYP3As in HepG2 and human fetal liver cells. Biol Pharm Bull 30:2091–2097

    Article  PubMed  CAS  Google Scholar 

  22. Luzio JP, Rous BA, Bright NA, Pryor PR, Mullock BM (2000) Lysosome-endosome fusion and lysosome biogenesis. J Cell Biol 113:1515–1524

    CAS  Google Scholar 

  23. Luzio JP, Mullock BM, Pryor PR, Lindsay MR, James DE, Piper RC (2001) Relationship between endosomes and lysosomes. Biochem Soc Trans 29:476–480

    Article  PubMed  CAS  Google Scholar 

  24. Ishibashi H, Komori A, Shimoda S, Gershwin ME (2007) Guidelines for therapy of autoimmune liver disease. Semin Liver Dis 27:214–226

    Article  PubMed  CAS  Google Scholar 

  25. Tilg H, Day CP (2007) Management strategies in alcoholic liver disease. Nat Clin Pract Gastroenterol Hepatol 4:24–34

    Article  PubMed  CAS  Google Scholar 

  26. Nakamura K, Nonaka H, Saito H, Tanaka M, Miyajima A (2004) Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology 39:635–644

    Article  PubMed  Google Scholar 

  27. Hamada T, Sato A, Hirano T, Yamamoto T, Son G, Onodera M, Torii I, Nishigami, Tanaka M, Miyajima A, Nishiguchi S, Fujimoto J, Tsujimura T (2007) Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosoamine in rats. Am J Pathol 171:872–881

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Tamihide Matsunaga, Mie Toba, Tsuyoshi Teramoto, Mitsue Mizuya, Kaori Aikawa & Shigeru Ohmori

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  1. Tamihide Matsunaga
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  2. Mie Toba
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  3. Tsuyoshi Teramoto
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  4. Mitsue Mizuya
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  5. Kaori Aikawa
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  6. Shigeru Ohmori
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Correspondence to Shigeru Ohmori.

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Matsunaga, T., Toba, M., Teramoto, T. et al. Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells. Med Mol Morphol 41, 53–58 (2008). https://doi.org/10.1007/s00795-007-0387-2

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  • DOI: https://doi.org/10.1007/s00795-007-0387-2

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