Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome.

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

TRPV4-Mediated Epithelial Junction Disruption in Allergic Rhinitis Triggered by House Dust Mites.

BACKGROUND: Epithelial barrier disruption is a crucial feature of allergic rhinitis (AR). Previous reports have indicated the role of transient receptor potential vanilloid (TRPV) 4 in regulating the intercellular junctions in various cells. However, the role of TRPV4 and its regulation by T helper 2 cell cytokines in the epithelial cells of patients with AR remains unclear. OBJECTIVE: We aimed to elucidate the expression of TRPV4 in nasal epithelial cells and its cytokine-induced regulation, and to reveal its role in house dust mite-induced junction disruption in AR. METHODS: The expression of TRPV4 in nasal epithelial cells was measured using real-time polymerase chain reaction, western blot, and immunohistochemical assays, and the expression levels were compared between the patients with AR and healthy controls. Altered expression of TRPV4 was induced in cultured nasal epithelial cells by stimulation of interleukin (IL) 4, IL-13, and tumor necrosis factor alpha. In addition, expression of E-cadherin and zonula occludens 1 was induced in Der p 1-stimulated epithelial cells by treatment with either a TRPV4 agonist (GSK1016790A) or a TRPV4 antagonist (RN1734). RESULTS: TRPV4 expression was increased in epithelial cells harvested from the affected turbinates compared to those from the normal turbinates. The stimulation of cultured epithelial cells with IL-4 and IL-13 resulted in TRPV4 upregulation. Additionally, E-cadherin and zonula occludens 1 expression levels decreased in the cultured epithelial cells treated with GSK1016790A after stimulation with Der p 1, whereas Der p 1 stimulation alone showed no effect on junctional protein expression. CONCLUSIONS: Increased TRPV4 expression occurred in epithelial cells harvested from patients with AR and epithelial cells stimulated by Th2 cytokines. Decreased junctional protein expression in epithelial cells after the stimulation by house dust mite allergen with TRPV4 agonist indicates a possible role of TRPV4 in the pathogenesis of allergen-induced epithelial barrier disruption in AR.