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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-14
pubmed:abstractText
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 E(2), 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, Ca(2+)-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 Ca(2+) mobilization from intracellular stores, whereas activation of 5-HTR3 induced Ca(2+) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-93
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Serotoninergic receptors on human airway epithelial cells.
pubmed:affiliation
University Hospital Freiburg, Department of Pneumology, Hugstetterstrasse 55, D-79106 Freiburg i Br, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't