Hyun Sil Lee1, Jean Kim. 1. Department of Medicine: Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Abstract
BACKGROUND: Cigarette smoke (CS) exposure has been shown to be associated with chronic rhinosinusitis (CRS). We hypothesized that that CS exposure results in impairment nasal epithelial cell growth and survival necessary for normal cell function. Furthermore, we hypothesized that normal nasal epithelial cell growth is dependent on vascular endothelial growth factor (VEGF) and that CS inhibits normal nasal epithelial cell growth and survival through VEGF-dependent mechanisms. METHODS: To examine whether nasal epithelial cell growth is dependent upon VEGF, we exposed in vitro cultures of human primary nasal epithelial cells (PNECs) from normal subjects to blocking antibodies against the VEGF co-receptor, neuropilin-1 (NP1), and measured cell growth using a proliferation assay. To study whether CS inhibits cell growth, we exposed PNECs to cigarette smoke extract (CSE). We also examined the ability of CSE exposure of PNECs to induce apoptosis. RESULTS: Exposure of PNECs from normal subjects to VEGF receptor anti-NP1 antibody resulted in inhibition of constitutive cell growth. CSE exposure resulted in dose-dependent inhibition of constitutive cell growth. Addition of anti-NP1 antibody to CSE-exposed cells resulted in no further inhibition of cell growth. CSE exposure also resulted in induction of apoptosis in a dose-dependent manner, comparable to that seen with VEGF blockade using anti-NP1 antibody. CONCLUSION: PNECs from normal healthy control subjects display VEGF-dependent constitutive cell growth. CSE impairs cell growth and promotes apoptosis of normal healthy nasal epithelial cells. The effect of CSE may occur in part through VEGF-dependent mechanisms.
BACKGROUND: Cigarette smoke (CS) exposure has been shown to be associated with chronic rhinosinusitis (CRS). We hypothesized that that CS exposure results in impairment nasal epithelial cell growth and survival necessary for normal cell function. Furthermore, we hypothesized that normal nasal epithelial cell growth is dependent on vascular endothelial growth factor (VEGF) and that CS inhibits normal nasal epithelial cell growth and survival through VEGF-dependent mechanisms. METHODS: To examine whether nasal epithelial cell growth is dependent upon VEGF, we exposed in vitro cultures of human primary nasal epithelial cells (PNECs) from normal subjects to blocking antibodies against the VEGF co-receptor, neuropilin-1 (NP1), and measured cell growth using a proliferation assay. To study whether CS inhibits cell growth, we exposed PNECs to cigarette smoke extract (CSE). We also examined the ability of CSE exposure of PNECs to induce apoptosis. RESULTS: Exposure of PNECs from normal subjects to VEGF receptor anti-NP1 antibody resulted in inhibition of constitutive cell growth. CSE exposure resulted in dose-dependent inhibition of constitutive cell growth. Addition of anti-NP1 antibody to CSE-exposed cells resulted in no further inhibition of cell growth. CSE exposure also resulted in induction of apoptosis in a dose-dependent manner, comparable to that seen with VEGF blockade using anti-NP1 antibody. CONCLUSION: PNECs from normal healthy control subjects display VEGF-dependent constitutive cell growth. CSE impairs cell growth and promotes apoptosis of normal healthy nasal epithelial cells. The effect of CSE may occur in part through VEGF-dependent mechanisms.