Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.
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.
Department of Medicine, Cork University Hospital, Cork, Ireland. oconnotm@mcmaster.ca
Terence M
TM
O'Connor
Joseph
J
O'Connell
Darren I
DI
O'Brien
Michael W
MW
Bennett
Triona
T
Goode
Louise
L
Burke
Charles P
CP
Bredin
Fergus
F
Shanahan
D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics* / Q000378:metabolism*; D012507:Sarcoidosis / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D003907:Dexamethasone