Author/Editor		Stegaev, V.; Sillat, T.; Porola, P.; Hännien, A.; Falus, A.; Mieliauskaite, D.; Buzás, E.; Rotar, Žiga; Mackiewicz, Z.; Stark, H.; Chazot, P. L.; Konttinen, Y.T.
Title		First identification of H[sub]4 histamine receptor in healthy salivary glands and in focal sialadenitis in Sjögren's syndrome
Type		članek
Vol. and No.		Letnik 64, št. 8
Publication year		2012
Volume		str. 2663-2668
ISSN		0004-3591 - Arthritis and rheumatism
Language		eng
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.
Keywords		histamine receptors autoimmune diseases Sjögren's syndrome receptorji histamina avtoimunske bolezni Sjögrenov sindrom