Hyun Ja Kwon

Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously

Viral upper respiratory tract infections are often followed by secondary bacterial infections in the form of acute rhinosinusitis. We investigate the effect of rhinovirus infection on the expression of cell adhesion molecules and bacterial adherence to primary human nasal epithelial cells.

Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells

Levocetirizine inhibits the production of intercellular adhesion molecule (ICAM)-1 and secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiologic changes related to human rhinovirus (HRV) infection. We investigated the effects of levocetirizine on rhinovirus infection in primary human nasal epithelial cells (HNEC) and A549 cells. Cells were treated with different concentrations of levocetirizine, ranging from 0.5, 5 or 50nM, either starting at the time of infection and continuing thereafter, or beginning 24h before infection and continuing thereafter. Levocetirizine treatment inhibited the HRV-induced increase in ICAM-1 mRNA and protein levels, as well as the HRV-induced expression of IL-6 and IL-8 mRNA and protein levels. Viral titer, as measured by culture in MRC-5 cells, was reduced by levocetirizine. Levocetirizine treatment also reduced the increased nuclear factor-kappa B (NF-kappaB) expression seen with HRV infection. Levocetirizine inhibited the expression of Toll-like receptor (TLR)3 mRNA and protein levels. These findings indicate that, in HNEC and A549 cells, levocetirizine inhibits HRV replication and HRV-induced upregulation of ICAM-1, IL-6, and IL-8, TLR3 expression and NF-kappaB activation. The results of this study suggest that levocetirizine may have a possible clinical application in the treatment of airway inflammation caused by HRV infection.

Staphylococcus aureus increases cytokine and matrix metalloproteinase expression in nasal mucosae of patients with chronic rhinosinusitis and nasal polyps.

Background Staphylococcus aureus is a common bacterial pathogen associated with chronic rhinosinusitis with/without nasal polyps (CRSw/sNP). We investigated the effect of S. aureus on the secretion of eotaxin, interleukin (IL)-5, IL-8, IL-13, matrix metalloproteinase (MMP) 2, MMP-9, and tissue inhibitor of MMP (TIMP) 1 in nasal mucosae from CRSwNP patients to assess the roles of these materials in NP pathogenesis. Methods We infected organ cultures of NP and inferior turbinate (IT) mucosae taken from patients with CRSwNP with S. aureus ATCC 25923 for 24 hours and incubated the cultures for an additional 48 hours at 37°C. S. aureus infection and staphylococcal enterotoxins were confirmed by real-time polymerase chain reaction. Eotaxin, IL-5, IL-8, IL-13, MMP-2, MMP-9, and TIMP-1 protein levels were measured by ELISA. Results S. aureus infection significantly increased the concentrations of eotaxin, IL-5, IL-8, and IL-13 in the IT and NP groups (p < 0.01 for all comparisons). S. aureus infection also significantly increased the concentrations of MMP-2, MMP-9, and TIMP-1 in both groups (p < 0.001 for all comparisons). After S. aureus infection, the relative increases in eotaxin (6.42 versus 3.56), IL-5 (15.29 versus 8.89), MMP-2 (1.95 versus 1.58), MMP-9 (2.34 versus 1.95), and TIMP-1 (1.45 versus 1.31) were greater in the NP group than in the IT group. Conclusion S. aureus infection enhances the secretion of cytokines, MMP-2, MMP-9, and TIMP-1 by both NPs and IT mucosae from patients with CRSwNP. S. aureus may play an important role in the pathogenesis of NP via tissue remodeling as well as eosinophilic inflammation.

Detection of parainfluenza virus 3 in turbinate epithelial cells of postviral olfactory dysfunction patients.

Objectives/Hypothesis: Postviral olfactory dysfunction (PVOD) develops after a common cold, but little is known about the viral pathogen inducing olfactory dysfunction. We hypothesized that human parainfluenza virus 3 (PIV3) may cause PVOD. We therefore assayed the nasal cavity mucosae of PVOD patients for the presence or persistence of PIV3.

Infection Rate and Virus-Induced Cytokine Secretion in Experimental Rhinovirus Infection in Mucosal Organ Culture: Comparison Between Specimens From Patients With Chronic Rhinosinusitis With Nasal Polyps and Those From Normal Subjects

OBJECTIVE To investigate the difference in susceptibility to rhinovirus (RV) infection and RV-induced inflammatory response between the nasal mucosae from patients with chronic rhinosinusitis with nasal polyps (CRS/NP) and subjects without CRS/NP (hereinafter, normal subjects). DESIGN In vitro study. SETTING Tertiary care rhinology clinic. PATIENTS We conducted RV infection experiments on the organ cultures of NPs and inferior turbinate mucosae from 16 patients with CRS/NP and sphenoid sinus and inferior turbinate mucosae from 19 patients who underwent transsphenoidal pituitary surgery. MAIN OUTCOME MEASURES Successful RV-16 infection was determined by positive identification of RV on the surface fluid of organ culture using seminested reverse transcriptase-polymerase chain reaction. Effects of RV on interleukin 6 (IL-6) and IL-8 secretion were measured by enzyme-linked immunosorbent assay. RESULTS The successful RV infection was achievable in 9 of 16 NP samples (56.3%) and 9 of 16 turbinate samples (56.3%) from patients with CRS/NP compared with 11 of 19 sphenoid sinus samples (57.9%) and 15 of 19 turbinate samples (78.9%) from normal subjects. The RV infection increased IL-6 and IL-8 secretion 236% and 173%, respectively, in NP samples, and 218% and 178%, respectively, in turbinate samples from patients with CRS/NP; compared with 231% and 145%, respectively, in sphenoid mucosa samples, and 181% and 148%, respectively, in turbinate samples from normal subjects. However, there were no statistical differences among the 4 groups. CONCLUSION These in vitro findings suggest that subjects with CRS/NP mucosa might not be more susceptible to RV infection, and did not secrete more cytokines in response to rhinovirus infection, than those with normal mucosa.

Asian sand dust enhances rhinovirus-induced cytokine secretion and viral replication in human nasal epithelial cells.

Context: Asian sand dust (ASD) originating in the arid deserts of Mongolia and China causes annual severe air pollution events in the Asia-Pacific area, including Korea, Japan, and China. ASD is thought to impact public health by aggravating or inducing respiratory illness. Among the most common respiratory illnesses is the common cold caused by rhinovirus (RV) infection. To date, however, the impact of ASD on RV infection has not been studied. Objective: In this study, we investigated the effect of ASD on RV infection in human nasal epithelial cells. Methods: Primary human nasal epithelial cells grown at an air-liquid interface were treated with ASD and/or RV. After RV infections were confirmed using semi-nested reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression and protein secretion of the inflammatory cytokines interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, and IL-8, indicators of the severity of RV-induced inflammation, were measured by real-time PCR and enzyme-linked immunosorbent assays. Viral titer was also assayed by culturing viruses to compare viral replication between RV-only and ASD-plus-RV groups. Results: ASD significantly increased RV-induced IFN-γ, IL-1β, IL-6, and IL-8 mRNA levels and protein secretion in primary nasal epithelial cells. In addition, ASD caused a significant increase in RV replication. Conclusions: Our results suggest that ASD may potentiate common cold symptoms associated with RV infection not only by enhancing IFN-γ, IL-1β, IL-6, and IL-8 secretion, but also by increasing viral replication.

Rhinovirus upregulates matrix metalloproteinase-2, matrix metalloproteinase-9, and vascular endothelial growth factor expression in nasal polyp fibroblasts.

Upregulation of matrix metalloproteinase (MMP) and vascular endothelial growth factor (VEGF) has been suggested to have an important role in the pathogenesis of nasal polyps (NPs). The aim of this study was to investigate the effect of rhinovirus (RV) infection on the expression of MMPs, tissue inhibitor of metalloproteinase (TIMP)‐1, and VEGF in NP fibroblasts.

Levocetirizine inhibits rhinovirus-induced bacterial adhesion to nasal epithelial cells through down-regulation of cell adhesion molecules

BACKGROUND The first critical step for bacterial infection is attachment of bacteria to the cell adhesion molecules of epithelial cells. The rhinovirus (RV)-induced increased expression of cell adhesion molecules including fibronectin (Fn) and carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) is closely related to the activation of nuclear factor-kappa B (NF-κB). Recent studies have demonstrated that Levocetirizine (LCT) has anti-inflammatory properties that are mediated by inhibitory effects on NF-κB in addition to classic antihistaminic effects. OBJECTIVE To investigate the inhibitory effects of LCT on the RV-induced expression of Fn and CEACAMs in human nasal epithelial cells (HNECs) and identified the effects of LCT on secondary Staphylococcus aureus and Haemophilus influenzae adhesion to RV-infected HNECs. METHODS Primary HNECs obtained from inferior turbinate mucosa were pretreated with 50 nM LCT 24 hours before RV-16 infection and for 48 hours thereafter. The expression levels of Fn and CEACAMs were assayed by real-time polymerase chain reaction (PCR) and Western blotting. Bacterial adhesion to cells was assessed by confocal microscopy. RESULTS Fibronectin and CEACAM messenger RNA (mRNA) and protein levels in HNECs were significantly increased by RV-16 infection. Levocetirizine significantly reduced these increases in mRNA levels and protein expression of Fn and CEACAMs. Confocal microscopy showed that treatment with LCT significantly reduced the adhesion levels of S aureus and H influenza in RV-infected HNECs compared with RV-infected, untreated HNECs. CONCLUSION These findings suggest that LCT inhibits the expression of Fn and CEACAMs and has the potential to prevent secondary bacterial infections in RV-infected HNECs by interfering with bacterial adhesion.

Clarithromycin inhibits rhinovirus-induced bacterial adhesions to nasal epithelial cells

We investigated the inhibitory effects of clarithromycin (CM) on the rhinovirus (RV)‐induced expression of fibronectin (Fn) and carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs), which act as major receptors for Staphylococcus aureus and Haemophilus influenzae, respectively. We further investigated the effects of CM on secondary S. aureus and H. influenzae adhesions to RV‐infected primary human nasal epithelial cells (HNECs).

The effect of a low concentration of hypochlorous acid on rhinovirus infection of nasal epithelial cells.

Background Low concentrations of hypochlorous acid (HOCl) have been shown to exhibit both antibacterial and anti-influenza virus activity, but HOCl still has not been used to kill human rhinovirus (HRV). To model the antiviral effect of nasal irrigation with low-level HOCl in patients with the common cold, we tested the effects of a low concentration of HOCl on HRV infection of primary human nasal epithelial cells (HNEC). Methods Cells were infected with HRV for 24 hours and treated with HOCl three times, for 5 minutes each time, at 12 hour intervals. The effects of HOCl on rhinovirus-induced secretion of IL-6 and IL-8 were assessed by ELISA and HRV replication was determined by viral titration. Results HOCl treatment significantly inhibited HRV-induced secretion of IL-6 and IL-8 and significantly reduced viral titer. The effects of HOCl peaked at 1 minute after HOCl generation and decreased thereafter. Conclusion These in vitro findings indicate that nasal irrigation with low-level HOCl solution may improve clinical symptoms in patients with the common cold.