Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Hdl Handle:
http://hdl.handle.net/10147/208979
Title:
Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.
Authors:
O'Connor, Terence M; O'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.ca
Citation:
J Clin Immunol. 2003 Sep;23(5):425-35.
Journal:
Journal of clinical immunology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/208979
PubMed ID:
14601651
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
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
ISSN:
0271-9142 (Print); 0271-9142 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Connor, Terence Men_GB
dc.contributor.authorO'Connell, Josephen_GB
dc.contributor.authorO'Brien, Darren Ien_GB
dc.contributor.authorBennett, Michael Wen_GB
dc.contributor.authorGoode, Trionaen_GB
dc.contributor.authorBurke, Louiseen_GB
dc.contributor.authorBredin, Charles Pen_GB
dc.contributor.authorShanahan, Fergusen_GB
dc.date.accessioned2012-02-03T15:09:02Z-
dc.date.available2012-02-03T15:09:02Z-
dc.date.issued2012-02-03T15:09:02Z-
dc.identifier.citationJ Clin Immunol. 2003 Sep;23(5):425-35.en_GB
dc.identifier.issn0271-9142 (Print)en_GB
dc.identifier.issn0271-9142 (Linking)en_GB
dc.identifier.pmid14601651en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208979-
dc.description.abstractSubstance 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshDexamethasone/pharmacologyen_GB
dc.subject.meshEpithelial Cells/drug effects/metabolismen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshLung/drug effects/*metabolism/*pathologyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshRNA, Messenger/genetics/metabolismen_GB
dc.subject.meshReceptors, Neurokinin-1/*genetics/*metabolismen_GB
dc.subject.meshSarcoidosis/*genetics/*metabolismen_GB
dc.subject.mesh*Up-Regulation/drug effectsen_GB
dc.titleUpregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.en_GB
dc.contributor.departmentDepartment of Medicine, Cork University Hospital, Cork, Ireland., oconnotm@mcmaster.caen_GB
dc.identifier.journalJournal of clinical immunologyen_GB
dc.description.provinceMunster-

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