Goblet Cells In Nasal Epithelium Research Articles

Prostaglandin E2 Receptor EP2, EP3, and EP4 Agonists Inhibit Antigen-Induced Mucus Hypersecretion in the Nasal Epithelium of Sensitized Rats

Prostaglandin (PG) E2 is a potential anti-inflammatory mediator that attenuates airway inflammation. To elucidate the functions of the PGE2 receptors (EP1, EP2, EP3, and EP4) in allergic inflammation, we examined the in vivo effects of EP agonists on mucus hypersecretion and eosinophil infiltration in rat nasal epithelium. We induced hypertrophic and metaplastic changes in goblet cells in nasal epithelium of ovalbumin-sensitized rats by intranasal challenge with ovalbumin. The effects of subcutaneous injections of EP agonists on mucus production and eosinophil infiltration were examined. The EP4 agonist (1 to 100 microg/kg) dose-dependently inhibited ovalbumin-induced mucus production. The EP2 and EP3 agonists (100 microg/kg) also significantly inhibited mucus production. The EP3 agonist inhibited antigen-induced eosinophil infiltration, whereas the EP1 agonist showed no effect. This suppression of mucus production by the EP4 agonist was only effective when the EP4 agonist was given in the effector phase; administration in the induction phase resulted in no effect. These results indicate that PGE2 acts as an anti-inflammatory mediator via the EP receptors of airways in allergic inflammation. Selective EP agonists may provide a new therapeutic strategy for airway mucus hypersecretion.

A mechanism of antigen-induced goblet cell degranulation in the nasal epithelium of sensitized rats

Background: We have produced hypertrophic and metaplastic changes of goblet cells in nasal epithelium of ovalbumin (OVA)-sensitized rats by intranasal challenge with OVA. A variety of allergic mediators and inflammatory cells are capable of stimulating goblet cell degranulation (epithelial mucus secretion); however, little is known about the mechanism by which antigen induces mucus hypersecretion. Objective: Our aim was to explain the mechanism of goblet cell degranulation in allergic inflammation. Methods: Antigen-induced goblet cell degranulation was evaluated by the transient decrease of epithelial mucosubstance 1 to 6 hours after intranasal challenge with OVA in nasal epithelium of OVA-sensitized rats. The effects of the H1-antagonist (d -chlorpheniramine malate), H2-antagonist (cimetidine), atropine, indomethacin, cysteinyl leukotriene (cysLT) antagonist (ONO1078), and antirat PMN antiserum on OVA-induced goblet cell degranulation were examined. Results: Goblet cell secretion 1 hour after OVA challenge was significantly inhibited by H1-antagonist, atropine, and cysLT antagonist, whereas the secretion 6 hours after the challenge was significantly inhibited by cysLT antagonist and antirat PMN antiserum. Circulating PMN cells and mucosal infiltrating eosinophils were completely abolished by antirat PMN antiserum. Conclusions: These results indicate the different mechanisms of goblet cell secretion between early-phase (1 hour after OVA challenge) and late-phase (6 hours after the challenge) reactions. Histamine stimulates early-phase secretion through the H1-receptor of cholinergic nerve terminals, and infiltrating inflammatory cells (eosinophils and/or neutrophils) play a role in late-phase secretion. CysLTs (leukotrienes C4, D4, and E4) are important for both early-phase and late-phase secretion. (J Allergy Clin Immunol 2003;112:119-25.)

Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells

Background: Mucus hypersecretion is a common response to inflammation in the lower airways and is a hallmark of chronic rhinitis. Objective: The purpose of this study was to elucidate the mechanisms of regranulation (mucus production) of goblet cells in nasal epithelium. Methods: Because neutrophils induce an epidermal growth factor (EGFR) cascade, we induced degranulation of goblet cells in rat nasal respiratory epithelium by means of intranasal inhalation of N-formyl-methionyl-leucyl-phenylalanine (fMLP), and we examined regranulation of the goblet cells and the role of EGFR inhibitors and neutrophils in the regranulation process. Results: In the control state Alcian blue/periodic acid–Schiff and mucin MUC5AC staining was present. Degranulation was induced in the nasal septal epithelium 4 hours after intranasal inhalation of fMLP (10–7 mol/L); 48 hours later, goblet-cell regranulation was complete. In the control state EGFR protein staining was absent in the epithelium, but after fMLP-induced degranulation, EGFR protein was expressed. After pretreatment with BIBX1522, a selective EGFR tyrosine kinase inhibitor, fMLP-induced degranulation was unaffected, but goblet-cell regranulation was prevented completely. Conclusion: These data suggest a role for the EGFR cascade in neutrophil-dependent production of goblet-cell mucins. Proving this theory will require the use of selective EGFR inhibitors in clinical studies of nasal hypersecretory states. (J Allergy Clin Immunol 2001;107:1046-50.)