Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.
Authors
O'Connor, Terence MO'Connell, Joseph
O'Brien, Darren I
Bennett, Michael W
Goode, Triona
Burke, Louise
Bredin, Charles P
Shanahan, Fergus
Affiliation
Department of Medicine, Cork University Hospital, Cork, Ireland., oconnotm@mcmaster.caIssue Date
2012-02-03T15:09:02ZMeSH
AdultCells, 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
Metadata
Show full item recordCitation
J Clin Immunol. 2003 Sep;23(5):425-35.Journal
Journal of clinical immunologyPubMed ID
14601651Abstract
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
engISSN
0271-9142 (Print)0271-9142 (Linking)
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