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Upregulation of Neurokinin-1 Receptor Expression in the Lungs of Patients with Sarcoidosis

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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-α 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.

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Authors and Affiliations

  1. Departments of Medicine and Pathology, Cork University Hospital, Cork, Ireland

    Terence M. O'Connor, Joseph O'Connell, Darren I. O'Brien, Michael W. Bennett, Triona Goode, Louise Burke, Charles P. Bredin & Fergus Shanahan

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  1. Terence M. O'Connor
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  2. Joseph O'Connell
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Correspondence to Terence M. O'Connor.

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O'Connor, T.M., O'Connell, J., O'Brien, D.I. et al. Upregulation of Neurokinin-1 Receptor Expression in the Lungs of Patients with Sarcoidosis. J Clin Immunol 23, 425–435 (2003). https://doi.org/10.1023/A:1025381803192

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