Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.
O'Connor, Terence M O'Connell, Joseph O'Brien, Darren I Bennett, Michael W Goode, Triona Burke, Louise Bredin, Charles P Shanahan, Fergus
O'Connor, Terence M
O'Connell, Joseph
O'Brien, Darren I
Bennett, Michael W
Goode, Triona
Burke, Louise
Bredin, Charles P
Shanahan, Fergus
Advisors
Editors
Other Contributors
Date
2012-02-03T15:09:02Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adult
Cells, Cultured
Dexamethasone/pharmacology
Epithelial Cells/drug effects/metabolism
Female
Humans
Immunohistochemistry
Lung/drug effects/*metabolism/*pathology
Male
RNA, Messenger/genetics/metabolism
Receptors, Neurokinin-1/*genetics/*metabolism
Sarcoidosis/*genetics/*metabolism
*Up-Regulation/drug effects
Cells, Cultured
Dexamethasone/pharmacology
Epithelial Cells/drug effects/metabolism
Female
Humans
Immunohistochemistry
Lung/drug effects/*metabolism/*pathology
Male
RNA, Messenger/genetics/metabolism
Receptors, Neurokinin-1/*genetics/*metabolism
Sarcoidosis/*genetics/*metabolism
*Up-Regulation/drug effects
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.
Language
eng
ISSN
0271-9142 (Print)
0271-9142 (Linking)
0271-9142 (Linking)
eISSN
ISBN
DOI
PMID
14601651