Skip to main content

Advertisement

SpringerLink
Log in

Disruption of the integrity of human peritoneal mesothelium by interleukin-1β and tumor necrosis factor-α

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Inflammatory and neoplastic disease processes of the abdominal cavity are frequently associated with disruption of the integrity of the peritoneal mesothelium. In the present study, we analyzed the effects of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the morphology and expression of adhesion molecules of human peritoneal mesothelial cells (HPMC). Treatment of HPMC with IL-1β and TNF-α resulted in a time- and dose-dependent alteration of the normal cobblestone morphology of the mesothelium with loss of polarization, cellular retraction and exposure of the submesothelial matrix. The effect was already observable after 6 h of treatment and was most pronounced at a dose of 10 ng/ml of IL-1β or TNF-α. These morphological alterations were associated with a significant rearrangement of the expression of mesothelial adhesion molecules as detected by flow cytometry. IL-1β and TNF-α both led to a loss of the expression of the hemidesmosomal integrin subunits α6 (P<0.01 and P<0.001) and β4 (P<0.01) and an increased expression of the integrin subunit α5 (P<0.001 and P<0.01). IL-1β furthermore upregulated the expression of the integrin subunits α1, α2 and the adhesion molecule CD44 while the latter was downregulated by TNF-α. Our data indicate that IL-1β and TNF-α may significantly affect disease processes of the abdominal cavity by their potential to disrupt the mesothelial basal cell-matrix adhesion and, thus, the integrity of the peritoneal mesothelial cell lining.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. Alt A, Ohba M, Li L, Gartsbein M, Belanger A, Denning MF, Kuroki T, Yuspa SH, Tennenbaum T (2001) Protein kinase C-delta-mediated phosphorylation of alpha6beta4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment. Cancer Res 61:4591–4598

    CAS  PubMed  Google Scholar 

  2. Amberger A, Maczek C, Jurgens G, Michaelis D, Schett G, Trieb K, Eberl T, Jindal S, Xu Q, Wick G (1997) Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins. Cell Stress Chaperones 2:94–103

    CAS  PubMed  Google Scholar 

  3. Andreoli SP, Mallett C, Williams K, McAteer JA, Rothlein R, Doerschuk CM (1994) Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney Int 46:1100–1109

    CAS  PubMed  Google Scholar 

  4. Bittinger F, Schepp C, Brochhausen C, Lehr HA, Otto M, Kohler H, Skarke C, Walgenbach S, Kirkpatrick CJ (1999) Remodeling of peritoneal-like structures by mesothelial cells: its role in peritoneal healing. J Surg Res 82:28–33

    Article  CAS  PubMed  Google Scholar 

  5. Borradori L, Sonnenberg A (1999) Structure and function of hemidesmosomes: more than simple adhesion complexes. J Invest Dermatol 112:411–418

    Google Scholar 

  6. Cannistra SA, Kansas GS, Niloff J, DeFranzo B, Kim Y, Ottensmeier C (1993) Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44. Cancer Res 53:3830–3838

    CAS  PubMed  Google Scholar 

  7. Carter D, True L, Otis CN (1997) Serous membranes: histology for pathologists. In: Sternberg SS (ed) Lippincott–Raven, New York, pp 2299–2328

  8. Casey RC, Burleson KM, Skubitz KM, Pambuccian SE, Oegema TR Jr, Ruff LE, Skubitz AP (2001) Beta 1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. Am J Pathol 159:2071–2080

    CAS  PubMed  Google Scholar 

  9. Cronauer MV, Stadlmann S, Klocker H, Abendstein B, Eder IE, Rogatsch H, Zeimet AG, Marth C, Offner FA (1999) Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells. Am J Pathol 155:1977–1984

    CAS  PubMed  Google Scholar 

  10. Dowling J, Yu QC, Fuchs E (1996) Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. J Cell Biol 134:559–572

    CAS  PubMed  Google Scholar 

  11. Giancotti FG, Ruoslahti E (1999). Integrin signaling. Science 285:1028–1032

    Article  CAS  PubMed  Google Scholar 

  12. Goodison S, Urquidi V, Tarin D (1999). CD44 cell adhesion molecules. Mol Pathol 52:189–196

    CAS  PubMed  Google Scholar 

  13. Hosono J, Narita T, Kimura N, Sato M, Nakashio T, Kasai Y, Nonami T, Nakao A, Takagi H, Kannagi R (1998) Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells. J Surg Oncol 67:77–84

    Article  CAS  PubMed  Google Scholar 

  14. Ikubo A, Morisaki T, Katano M, Kitsuki H, Anan K, Uchiyama A, Tanaka M, Torisu M (1995) A possible role of TGF-beta in the formation of malignant effusions. Clin Immunol Immunopathol 77:27–32

    CAS  PubMed  Google Scholar 

  15. Klaus A, Margreiter R, Pernthaler H, Klima G, Offner FA (2003) Diffuse mesenterial sclerosis: a characteristic feature of chronic small-bowel allograft rejection. Virchows Arch 442:48–55

    PubMed  Google Scholar 

  16. Kutteh WH, Kutteh CC (1992) Quantitation of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in the effusions of ovarian epithelial neoplasms. Am J Obstet Gynecol 167:1864–1869

    CAS  PubMed  Google Scholar 

  17. Lessan K, Aguiar DJ, Oegema T, Siebenson L, Skubitz AP (1999) CD44 and beta1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells. Am J Pathol 154:1525–1537

    CAS  PubMed  Google Scholar 

  18. Li FK, Davenport A, Robson RL, Loetscher P, Rothlein R, Williams JD, Topley N (1998) Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression. Kidney Int 54:2170–2183

    Article  CAS  PubMed  Google Scholar 

  19. Mandl-Weber S, Cohen CD, Haslinger B, Kretzler M, Sitter T (2002) Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cells. Kidney Int 61:570–578

    Article  CAS  PubMed  Google Scholar 

  20. Margetts PJ, Kolb M, Yu L, Hoff CM, Holmes CJ, Anthony DC, Gauldie J (2002) Inflammatory cytokines, angiogenesis, and fibrosis in the rat peritoneum. Am J Pathol 160:2285–2294

    CAS  PubMed  Google Scholar 

  21. Nagy JA, Morgan ES, Herzberg KT, Manseau EJ, Dvorak AM, Dvorak HF (1995) Pathogenesis of ascites tumor growth: angiogenesis, vascular remodeling and stroma formation in the peritoneal lining. Cancer Res 55:376–385

    CAS  PubMed  Google Scholar 

  22. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271–279

    CAS  PubMed  Google Scholar 

  23. Nishimura S, Chung YS, Yashiro M, Inoue T, Sowa M (1996) CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cells. Jpn J Cancer Res 87:1235–1244

    CAS  PubMed  Google Scholar 

  24. Offner FA, Obrist P, Stadlmann S, Feichtinger H, Klingler P, Herold M, Zwierzina H, Hittmair A, Mikuz G, Abendstein B, Zeimet A, Marth C (1995) IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells. Cytokine 7:542–547

    Article  CAS  PubMed  Google Scholar 

  25. Offner FA, Feichtinger H, Stadlmann S, Obrist P, Marth C, Klingler P, Grage B, Schmahl M, Knabbe C (1996) Transforming growth factor-β synthesis by human peritoneal mesothelial cells. Induction by interleukin-1. Am J Pathol 148:1679–1688

    CAS  PubMed  Google Scholar 

  26. Propst T, Propst A, Herold M, Schauer G, Judmaier G, Braunsteiner H, Stoffler G, Vogel W (1993) Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid. Eur J Clin Invest 23:832–836

    CAS  PubMed  Google Scholar 

  27. Runyon BA, Hillebrand DJ (1998) Surgical peritonitis and other diseases of the peritoneum, mesentery, momentum, and diaphragm. In: Feldman M, Scharschmidt BF, Sleisenger MH (eds) Gastrointestinal and liver disease. Pathophysiology, diagnosis, management. Saunders, Philadelphia, pp 2035–2046

  28. Ruoslahti E, Vaheri A (1997). Cell-to-cell contact and extracellular matrix. Curr Opin Cell Biol 9:605–607

    Article  CAS  PubMed  Google Scholar 

  29. Sachs L (1997) Angewandte statistik. In: Sachs L (ed) Anwendung statistischer methoden. Springer, Berlin Heidelberg New York, pp 335–337

  30. Skubitz AP, Bast RCJr, Wayner EA, Letourneau PC, Wilke MS (1996) Expression of alpha 6 and beta 4 integrins in serous ovarian carcinoma correlates with expression of the basement membrane protein laminin. Am J Pathol 148:1445–1461

    CAS  PubMed  Google Scholar 

  31. Sriram PS, Mohammed KA, Nasreen N, Hardwick J, Van Horn R, Sanders K, Antony VB (2002) Adherence of ovarian cancer cells induces pleural mesothelial cell (PMC) permeability. Oncol Res 13:79–85

    CAS  PubMed  Google Scholar 

  32. Strobel T, Cannistra SA (1999) Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol Oncol 73:362–367

    Article  CAS  PubMed  Google Scholar 

  33. Tietze L, Borntraeger J, Klosterhalfen B, Amo-Takyi B, Handt S, Gunther K, Merkelbach-Bruse S (1999) Expression and function of beta(1) and beta(3) integrins of human mesothelial cells in vitro. Exp Mol Pathol 66:131–139

    Article  CAS  PubMed  Google Scholar 

  34. Topley N (1995) The cytokine network controlling peritoneal inflammation. Perit Dial Int 15:35–40

    Google Scholar 

  35. Topley N, Joerres A, Luttmann W, Petersen MM, Lang J, Thierauch KH, Muller C, Coles GA, Davies M, Williams JD (1993) Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1β and TNFα. Kidney Int 43:226–233

    Google Scholar 

  36. Topley N, Brown Z, Joerres A, Westwick J, Davies M, Coles GA, Williams JD (1993) Human peritoneal mesothelial cells synthesize interleukin-8: synergistic induction by interleukin-1 beta and tumor necrosis factor-alpha. Am J Pathol 142:1876–1886

    Google Scholar 

  37. Van Rossen ME, Hofland LJ, van den Tol MP, van Koetsveld PM, Jeekel J, Marquet RL, van Eijck CH (2001) Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum. J Pathol 193:530–537

    Article  PubMed  Google Scholar 

  38. Volz J, Volz-Koster S, Kanis S, Klee D, Ahlert C, Melchert F (2000) Modulation of tumor-induced lethality after pneumoperitoneum in a mouse model. Cancer 89:262–266

    Article  CAS  PubMed  Google Scholar 

  39. Whitaker D, Papadimitriou J (1985) Mesothelial healing: morphological and kinetic investigations. J Pathol 145:159–175

    CAS  PubMed  Google Scholar 

  40. Witz CA, Montoya-Rodriguez IA, Miller DM, Schneider BG, Schenken RS (1998) Mesothelium expression of integrins in vivo and in vitro. J Soc Gynecol Invest 5:87–93

    Article  CAS  Google Scholar 

  41. Zeimet AG, Widschwendter M, Knabbe C, Fuchs D, Herold M, Muller-Holzner E, Daxenbichler G, Offner FA, Dapunt O, Marth C (1998) Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer. J Clin Oncol 16:1861–1868

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The excellent technical assistance of Mrs. I. Jehart is gratefully acknowledged. We would also like to thank Mr. J. Pollheimer for helpful comments on statistics.

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Innsbruck, 6020, Innsbruck, Austria

    Sylvia Stadlmann, Ruth Raffeiner, Patrizia Lucia Moser & Gregor Mikuz

  2. Tyrolean Cancer Research Institute, 6020, Innsbruck, Austria

    Albert Amberger

  3. Department of Transplant Surgery, D. Swarovski Research Laboratory, University Hospital Innsbruck, 6020, Innsbruck, Austria

    Raimund Margreiter

  4. Department of Obstetrics and Gynecology, University of Innsbruck, 6020, Innsbruck, Austria

    Alain Gustave Zeimet

  5. Department of Obstetrics and Gynecology, Hospital Hall, 6060, Hall in Tirol, Austria

    Burkhardt Abendstein

  6. Institute of Pathology, RWTH-Aachen, 52062, Aachen, Germany

    Bernd Klosterhalfen

  7. Institute of Pathology, Academic Teaching Hospital Feldkirch, 6800, Feldkirch, Austria

    Felix Albert Offner

Authors
  1. Sylvia Stadlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruth Raffeiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Albert Amberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raimund Margreiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alain Gustave Zeimet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Burkhardt Abendstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patrizia Lucia Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gregor Mikuz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bernd Klosterhalfen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Felix Albert Offner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Felix Albert Offner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stadlmann, S., Raffeiner, R., Amberger, A. et al. Disruption of the integrity of human peritoneal mesothelium by interleukin-1β and tumor necrosis factor-α. Virchows Arch 443, 678–685 (2003). https://doi.org/10.1007/s00428-003-0867-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-003-0867-2

Keywords

Search

Navigation