Search

Objectives: Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin‐binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. Study design: In vivo and in vitro. Methods: We investigated the effects of CDH26 knockdown by lentivirus (LV)‐mediated shRNA on ovalbumin (OVA)‐induced AR mice and IL‐13‐stimulated human nasal epithelial cells (NECs). Results: CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV‐shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA‐specific IgE, IgG, pro‐inflammatory factors IL‐25, IL‐33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR‐induced Th2 inflammation, LV‐shCDH26 intervention effectively decreased the distribution of CD4+/GATA3+ Th2 cells, and the mRNA expression of IL‐4, IL‐5, and IL‐13 in the nasal mucosa. CDH26 knockdown down‐regulated the expression of β‐catenin but not for E‐cadherin and ZO‐1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM‐CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL‐13‐induced NECs. Conclusions: CDH26 knockdown attenuates the AR‐induced inflammatory response both in vivo and in vitro. Level of Evidence: NA Laryngoscope, 133:1558–1567, 2023 [ABSTRACT FROM AUTHOR]

Objective: Rhinoviruses (RV), which are responsible for the majority of common colds, induce mucus overproduction, increased vascular permeability, and secondary bacterial infection. These symptoms are primarily caused by barrier function disruption, which is controlled by intercellular junctions. In this study, we investigated whether reactive oxygen species (ROS) are closely involved in tight junction disruption of primary human nasal epithelial (HNE) cells induced by infection of RV .Methods and Results: Incubation with RV resulted in disruption of tight junction proteins (ZO-1, E-cadherin, claudin-1, and occludin) in HNE cells. Pretreatment with diphenylene iodonium (DPI) decreased RV-induced disruption of tight junction in HNE cells. RV-induced generation of ROS was diminished by DPI. However, rotenone was not inhibited in HNE cells following incubation with RV. Rhinoviruses resulted in a marked decrease in protein phosphatases activity and an increase in protein tyrosine phosphorylation levels in HNE cells. Diphenylene iodonium inhibited the RV-induced inactivation of phosphatases and phosphorylation of protein tyrosine. In addition, inhibition of protein tyrosine phosphatases with phenylarsine oxide resulted in a marked decrease in protein phosphatase activity and disruption of tight junction proteins in HNE cells.Conclusion: Our results suggest that ROS-mediated inhibition of phosphatases plays a crucial role in disruption of tight junctions in HNE cells by RV. The data suggest that RV infection may damage nasal epithelial barrier function.Level Of Evidence: NA Laryngoscope, 128:E393-E401, 2018. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: 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). Methods: Cells were pretreated with 10 μM CM 24 hours before RV-16 infection and for 48 hours thereafter. The expression levels of Fn and CEACAMs were assayed by reverse transcriptase-polymerase chain reaction and Western blotting. Bacterial adhesion to cells was assessed by confocal microscopy and the fluorescence intensity of adherent bacteria was analyzed using Image-Pro Plus 5.1 (Media Cybernetics, Bethesda, MD). Results: Clarithromycin significantly inhibited the RV-induced gene and protein expression of Fn and CEACAMs in HNECs. Compared with RV-infected cells, CM treatment significantly reduced the adhesion levels of S. aureus and H. influenzae in RV-infected HNECs to the levels seen in noninfected control cells. Conclusions: These findings indicate that CM has the potential to prevent secondary bacterial infections in RV-infected HNECs by inhibiting the expression of Fn and CEACAM, thereby interfering with bacterial adhesion. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: 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. Methods: Cells were infected with rhinovirus serotype 16 (RV-16), and then Staphylococcus aureus, Streptococcus pneumoniae, or Hemophilus influenzae were added to the culture. Rhinovirus-induced expression of fibronectin, platelet-activating factor receptor, and carcinoembryonic antigen-related cell adhesion molecule, was assayed by confocal microscopy, real-time polymerase chain reaction, and Western blot analysis. Bacterial adhesion to cells was assessed by confocal microscopy and the fluorescence intensity of adherent bacteria was analyzed using Image-Pro Plus 5.1 (Media Cybernetics, Inc., Bethesda, MD). Results: RV-16 infection significantly increased the gene and protein expression of fibronectin, platelet-activating factor receptor, and carcinoembryonic antigen-related cell adhesion molecule in nasal epithelial cells. Compared with rhinovirus-uninfected control cells, the adhesion of S. aureus, S. pneumoniae, and H. influenzae increased significantly to 2.53-fold, 1.51-fold, and 2.74-fold of control levels, respectively, in rhinovirus-infected nasal epithelial cells. Conclusions: These findings suggest that increased expression of host cell adhesion molecules may be the mechanism accounting for the increase in susceptibility to bacterial rhinosinusitis associated with rhinovirus-induced upper respiratory infections. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]