This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0151OCv1 36/1/85    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bayer, H. Articles by Idzko, M. Search for Related Content PubMed PubMed Citation Articles by Bayer, H. Articles by Idzko, M.

Serotoninergic Receptors on Human Airway Epithelial Cells

Hans Bayer^*, Tobias Müller^*, Daniel Myrtek, Stephan Sorichter, Manfred Ziegenhagen, Johannes Norgauer, Gernot Zissel and Marco Idzko

Department of Pneumology, University Hospital Freiburg; Wilhelm-Anton-Hospital, Goch; and Department of Dermatology, University of Jena, Jena, Germany

Correspondence and requests for reprints should be addressed to Dr. Marco Idzko, University Hospital Freiburg, Department of Pneumology, Hugstetterstraße 55, D-79106 Freiburg i. Br., Germany. E-mail: idzko{at}med1.ukl.uni-freiburg.de

There is accumulating evidence that points to a role of serotonin (5-hydroxytryptamine [5-HT]) in the pathophysiology of asthma. Therefore, we analyzed the expression of serotoninergic receptors (5-HTR), its linkage to intracellular calcium homeostasis, and its influence on the production and secretion of IL-6, prostaglandin E₂, the CCL-Chemokine CCL5/Rantes, and the CXC-chemokines CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC in primary alveolar epithelial cells type II and the human lung cell lines A549 and BEAS-2B. Employing a PCR approach we were able to demonstrate mRNA expression of several 5-HTR, such as the heptahelical receptors 5-HTR1A, 5-HTR1B, 5-HTR1E, 5-HTR1F, 5-HTR2A, 5-HTR4, 5-HTR6, and 5-HTR7, as well as the ligand-gated ion channel 5-HTR3 in alveolar epithelial cells type II (AEC-II), A549, and BEAS-2B cells. To verify functional expression of 5-HTR subtypes, Ca²⁺-transients were analyzed. This enabled us to show that 5-HT induced an increase in intracellular calcium. Further experiments with isotype-selective receptor agonists allowed us to demonstrate that 5-HT induced calcium transients via activation of 5-HTR1, 5-HTR2, and 5-HTR3 in A549 and BEAS-2B cells. Moreover, we revealed that stimulation of 5-HTR1 and 5-HTR2 induced Ca²⁺ mobilization from intracellular stores, whereas activation of 5-HTR3 induced Ca²⁺ influx from the extracellular space. Functional studies indicated that activation of 5-HTR1B, 5-HTR1E/F, 5-HTR2, 5-HTR3, 5-HTR4, and 5-HTR7 regulated the release of the cytokine IL-6 and the CXC-chemokine CXCL8/IL-8. Our study shows that 5-HT stimulates different signaling pathways and regulates cytokine release in airway epithelial cells. In summary, our data implicate a pathophysiologic role of 5-HT in the asthmatic inflammatory responses in human airway epithelial cells.

Key Words: airway epithelial cells • Ca²⁺-homeostasis • cytokine release • serotonin • serotoninergic receptors

This article has been cited by other articles:

				R. J. Van Lieshout, J. Bienenstock, and G. M. MacQueen A Review of Candidate Pathways Underlying the Association Between Asthma and Major Depressive Disorder Psychosom Med, February 1, 2009; 71(2): 187 - 195. [Abstract] [Full Text] [PDF]

				A. V. Andreeva, M. A. Kutuzov, and T. A. Voyno-Yasenetskaya Regulation of surfactant secretion in alveolar type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L259 - L271. [Abstract] [Full Text] [PDF]

				B. M. Rotoli, V. Dall'Asta, A. Barilli, R. D'Ippolito, A. Tipa, D. Olivieri, G. C. Gazzola, and O. Bussolati Alveolar Macrophages from Normal Subjects Lack the NOS-Related System y+ for Arginine Transport Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 105 - 112. [Abstract] [Full Text] [PDF]