Source:http://linkedlifedata.com/resource/pubmed/id/16873768
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-12-14
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1044-1549
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
85-93
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pubmed:meshHeading |
pubmed-meshheading:16873768-Biological Transport, Active,
pubmed-meshheading:16873768-Calcium,
pubmed-meshheading:16873768-Cells, Cultured,
pubmed-meshheading:16873768-Dinoprostone,
pubmed-meshheading:16873768-Epithelial Cells,
pubmed-meshheading:16873768-Humans,
pubmed-meshheading:16873768-Interleukin-6,
pubmed-meshheading:16873768-Interleukin-8,
pubmed-meshheading:16873768-Receptors, Serotonin,
pubmed-meshheading:16873768-Respiratory Mucosa
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pubmed:year |
2007
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pubmed:articleTitle |
Serotoninergic receptors on human airway epithelial cells.
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pubmed:affiliation |
University Hospital Freiburg, Department of Pneumology, Hugstetterstrasse 55, D-79106 Freiburg i Br, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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