Skip to main content

Advertisement

SpringerLink
Log in

Production of adrenomedullin from synovial cells in rheumatoid arthritis patients

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

It was recently reported that plasma levels of adrenomedullin (AM), identified as a vasorelaxant peptide, are significantly higher in rheumatoid arthritis (RA) patients than in osteoarthritis (OA) patients. The objective of the present study was to elucidate AM production in synovial cells from patients with RA. Adrenomedullin mRNA was detected in cultured synovial cells from RA patients by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical analysis demonstrated the presence of AM in synovial cells from RA patients. In addition, we investigated AM levels in knee joint fluids from RA and OA patients. Those from RA patients were elevated approximately threefold over those of OA patients. In this study, we demonstrated for the first time AM expression in synovial cells from RA patients and high levels of AM production in RA joint fluid.

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.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. Arend WP, Dayer J-M (1990) Cytokines and cytokines inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum 33:305–315

    CAS  PubMed  Google Scholar 

  2. Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T (1993) Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 192:553–560

    CAS  PubMed  Google Scholar 

  3. Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, Eto T (1993) Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol 241:271–273

    Article  CAS  PubMed  Google Scholar 

  4. Ishimitsu T, Nishikimi T, Saito Y, Kitamura K, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H (1994) Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. J Clin Invest 94:2158–2164

    CAS  PubMed  Google Scholar 

  5. Jougasaki M, Wei CM, McKinley LJ, Burnett JC Jr (1995) Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation 92: 286–289

    CAS  PubMed  Google Scholar 

  6. Sugo S, Minamino N, Kangawa K, Miyamoto K, Kitamura K, Sakata J, Eto T, Matsuo H (1994) Endothelial cells synthesize and secrete adrenomedullin. Biochem Biophys Res Commun 201:1160–1166

    CAS  PubMed  Google Scholar 

  7. Sugo S, Minamino N, Shoji H, Kangawa K, Kitamura K, Eto T, Matsuo H (1995) Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem Biophys Res Commun 207:25–32

    Article  CAS  PubMed  Google Scholar 

  8. Isumi Y, Shoji H, Sugo S, Tochimoto T, Yoshioka M, Kangawa K, Matsuo H, Minamino N (1998) Regulation of adrenomedullin production in rat endothelial cells. Endocrinology 139:838–846

    CAS  PubMed  Google Scholar 

  9. Tomoda Y, Isumi Y, Katafuchi T, Minamino N (2001) Regulation of adrenomedullin secretion from cultured cells. Peptides 22:1783–1794

    Article  CAS  PubMed  Google Scholar 

  10. Isumi Y, Minamino N, Katafuchi T, Yoshioka M, Tsuji T, Kangawa K, Matsuo H. (1998) Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells. Endocrinology 139:2552–2563

    CAS  PubMed  Google Scholar 

  11. Kohase M, May LT, Tamm I, Vilcek J, Sehgal PB (1987) A cytokine network in human diploid fibroblasts: interaction of beta-interferons, tumor necrosis factor, plate-derived growth factor, and interleukin-1. Mol cell Biol 7:273–280

    CAS  PubMed  Google Scholar 

  12. Helfgott DC, May LT, Sthoeger Z, Tammn I, and Sehgal PB (1987) Bacterial lipopolysaccharide (endotoxin) enhances and expression and secretion of beta2 interferon by human fibroblasts. J Exp Med 166:1300–1309

    CAS  PubMed  Google Scholar 

  13. Newton RC, Covington M (1987) The activation of human fibroblasts prostaglandin E production by interleukin 1. Cell Immunol 110:338–349

    CAS  PubMed  Google Scholar 

  14. Isumi Y, Minamino N, Kubo A, Nishimoto N, Yoshizaki K, Yoshioka M, Kangawa K, Matsuo H. (1998) Adrenomedullin stimulates interleukin-6 production in Swiss 3T3 cells. Biochem Biophys Res Commun 244:325–321

    Article  CAS  PubMed  Google Scholar 

  15. Yudoh K, Matsuno H, Kimura T. (1999) Plasma adrenomedullin in rheumatoid arthritis compared with other rheumatic disease. Arthritis Rheum 42:1297–1303

    Article  CAS  PubMed  Google Scholar 

  16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    CAS  PubMed  Google Scholar 

  17. Kellegren JH, Lawrence JS (1957) radiological assessment of osteoarthrosis. Ann Rheum Dis 16:494–502

    CAS  Google Scholar 

  18. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem 183:156–159

    Google Scholar 

  19. Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuo H, Kangawa K (1997) Cardiac production and secretion of adrenomedullin are increased in heart failure. Hypertension 30:1369–1375

    CAS  PubMed  Google Scholar 

  20. Nanke Y, Kotake S, Yonemoto K, Saito S, Tomatsu T, Kamatani N (2003) Adrenomedullin in synovial fluids from patients with rheumatoid arthritis inhibits interleukin 6 production from synoviocytes. Ann Rheum Dis 62:82–83

    Article  CAS  PubMed  Google Scholar 

  21. Kolb H, Kolb-Bachofen V (1992) Nitric oxide: a pathogenetic factor in autoimmunity. Immunol Today 13:157–160

    CAS  PubMed  Google Scholar 

  22. Oyanagui Y (1994) Nitric oxide and superoxide radicals are involved in both initiation and development of adjuvant arthritis in rats. Life Sci 54:285–289

    Article  Google Scholar 

  23. Ueki Y, Miyake S, Tominaga Y, Eguchi K. (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J Rheumatol 23:230–236

    CAS  PubMed  Google Scholar 

  24. Ikeda U, Kanbe T, Kawahara Y, Yokoyama M, Shimada K. (1996) Adrenomedullin augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes. Circulation 94:2560–2565

    CAS  PubMed  Google Scholar 

  25. Ikeda U, Kambe T, Shimada K (1996) Adrenomedullin increases inducible nitric oxide synthase in rat vascular smooth muscle cells stimulated with interleukin-1. Hypertension 27:1240–1244

    CAS  PubMed  Google Scholar 

  26. Shimekake Y, Nagata K, Ohta S, Kambayashi Y, Teraoka H, Kitamura K, Eto T, Kangawa K, Matsuo H (1995) Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells. J Biol Chem 270:4412–4417

    Article  CAS  PubMed  Google Scholar 

  27. Kato H, Shichiri M, Marumo F, Hirata Y (1997) Adrenomedullin as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. Endocrinology 138:2615–2620

    CAS  PubMed  Google Scholar 

  28. Kamoi H, Kanazawa H, Hirata K, Kurihara N, Yano Y, Otani S (1995) Adrenomedullin inhibits the secretion of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, from rat alveolar macrophages. Biochem Biophys Res Commun 211:1031–1035

    CAS  PubMed  Google Scholar 

  29. Kubo A, Minamino N, Isumi Y, Katafuchi T, Kangawa K, Dohi K, Matsuo H (1998) Production of adrenomedullin in a macrophage cell line and peritoneal macrophage. J Biol Chem 273:16730–16738

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku Kobe, Hyogo 650-0017, Japan

    T. Matsushita, N. Matsui, S. Yoshiya, H. Fujioka & M. Kurosaka

Authors
  1. T. Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Yoshiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Fujioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Kurosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Matsui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsushita, T., Matsui, N., Yoshiya, S. et al. Production of adrenomedullin from synovial cells in rheumatoid arthritis patients. Rheumatol Int 24, 20–24 (2004). https://doi.org/10.1007/s00296-003-0315-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-003-0315-2

Keywords

Search

Navigation