During inflammatory states, airway epithelial cells are stimulated by various proinflammatory mediators to synthesize paracrine mediators including prostaglandin E2, which likely contributes to the recurrence of allergic inflammation. We studied the effects of acetylcholine (ACh) and substance P (SP) on PGE2 release because these two neuromediators are widely involved in airway inflammation, e.g., to trigger mucosal vasodilation and plasma exudation. PGE2 release was studied at baseline and after addition of ACh and SP (10−10 to 10−7 M) in primary cultures of human nasal epithelial cells from control mucosa, inflammatory non-atopic mucosa, and inflammatory atopic mucosa. The mediators' effects on COX 2 mRNA were assessed by Northern blotting. We also tested the effect of atropine and SRI40333, inhibitors of ACh and SP, respectively. The spontaneous release of PGE2 was about three times higher in cells from atopic subjects. ACh and SP markedly increased PGE2 release (by more than 1.5 times) and this effect was similar whether the sampled tissues were inflammatory or not. In cells from atopic subjects this neuromediator effect led to a fivefold increase in PGE2 release, as compared to baseline production by cells from control mucosa. This stimulation of PGE2 release by neural mediators was inhibited by specific antagonists. ACh and SP increased COX 2 mRNA in the three groups. Thus, neuromediators can bolster PGE2 production in the airway, likely reinforcing inflammation. In conclusion, these data provide evidence that the interplay of nerve fibers and airway epithelial cells is likely important in inflammatory conditions as, e.g., allergy and asthma.
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