Sjögren's Syndrome

Brief Report: First identification of H4 histamine receptor in healthy salivary glands and in focal sialadenitis in Sjögren's syndrome

  1. V. Stegaev1,
  2. T. Sillat2,
  3. P. Porola3,
  4. A. Hänninen4,
  5. A. Falus5,
  6. D. Mieliauskaite6,
  7. E. Buzás5,
  8. Z. Rotar7,
  9. Z. Mackiewicz8,
  10. H. Stark9,
  11. P. L. Chazot10,
  12. Y. T. Konttinen11,*

Article first published online: 27 JUL 2012

DOI: 10.1002/art.34484

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 64, Issue 8, pages 2663–2668, August 2012

Additional Information

How to Cite

Stegaev, V., Sillat, T., Porola, P., Hänninen, A., Falus, A., Mieliauskaite, D., Buzás, E., Rotar, Z., Mackiewicz, Z., Stark, H., Chazot, P. L. and Konttinen, Y. T. (2012), Brief Report: First identification of H4 histamine receptor in healthy salivary glands and in focal sialadenitis in Sjögren's syndrome. Arthritis & Rheumatism, 64: 2663–2668. doi: 10.1002/art.34484

Author Information

  1. 1

    University of Helsinki, Helsinki, Finland

  2. 2

    Orton Orthopedic Hospital of the Orton Foundation, Helsinki, Finland

  3. 3

    Coxa Hospital for Joint Replacement, Tampere, Finland

  4. 4

    University of Turku, Turku, Finland

  5. 5

    Semmelweis University, Budapest, Hungary

  6. 6

    State Research Institute Center for Innovative Medicine, Vilnius, Lithuania

  7. 7

    Medical Centre of Ljubljana, Ljubljana, Slovenia

  8. 8

    Medical University of Bialystok, Bialystok, Poland

  9. 9

    Goethe University, Frankfurt, Germany

  10. 10

    Durham University, Durham, UK

  11. 11

    University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

*Institute of Clinical Medicine, Department of Medicine, Biomedicum 1, Helsinki University Central Hospital, PO Box 700, Helsinki FIN-00029, Finland

Publication History

  1. Issue published online: 27 JUL 2012
  2. Article first published online: 27 JUL 2012
  3. Accepted manuscript online: 5 APR 2012 11:46AM EST
  4. Manuscript Accepted: 22 MAR 2012
  5. Manuscript Received: 5 APR 2011

Funded by

  • European Union (European Cooperation in Science and Technology [COST]
  • Action BM0806 on Histamine 4 Receptor
  • Finska Läkaresällskapet
  • Sigrid Juselius Foundation
  • Orton Invalid Foundation
  • Hospital District of Helsinki and Uusimaa (EVO grants)
  • Academy of Finland
  • Center for International Mobility
  • Danish Council for Strategic Research
  • European Science Foundation Research Networking Programme in Medical Sciences (Regenerative Medicine)
  • Neuronal Coordination Research Focus Frankfurt (NeFF) project
  • Hessen LOEWE program
  • Oncogenic Signaling Frankfurt (OSF)
  • Royal College of Anaesthesia and the Biotechnology and Biological Sciences Research Council (UK)

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Abstract

Objective

The conventional H1 and H2 histamine receptors have >10,000-fold lower avidity for histamine than H4 histamine receptor, which has been implicated in autoimmune diseases. This study was undertaken to compare H4 histamine receptor levels in the salivary glands (SGs) of healthy controls with those in the SGs of patients with primary Sjögren's syndrome (SS).

Methods

H4 histamine receptor messenger RNA (mRNA) was analyzed using real-time quantitative polymerase chain reaction, and the receptor protein was examined using immunostaining. Effects of the H4 histamine receptor agonist ST-1006 on cytokine synthesis by human SG (HSG) cells were analyzed using xMAP technology and enzyme-linked immunosorbent assay.

Results

Healthy SGs contained H4 histamine receptor mRNA. The receptor protein was localized to the acinar and ductal epithelial cells. H4 histamine receptor agonist stimulated HSG cells to produce the cytokines interleukin-8 and vascular endothelial growth factor. SS patients had low H4 histamine receptor levels.

Conclusion

H1 and H2 histamine receptor antagonists are not effective in the treatment of autoimmune diseases. However, such antagonists do not affect the newly discovered H4 histamine receptor. Dendritic cells and lymphocytes are nonprofessional histamine-producing cells, which produce histamine at 100–1,000-fold lower rates than mast cells do. Saliva contains only 0.31–12.4 ng/ml histamine, which is too low to stimulate H1 or H2 histamine receptor, but stimulates H4 histamine receptor half maximally. Our findings show that H4 histamine receptor is strongly expressed in tubuloacinar SG cells, which emphasizes the role of these cells in the pathogenesis of SS.

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