Cholinergic stimulation attenuates the IL-4 induced expression of E-selectin and vascular endothelial growth factor by equine pulmonary artery endothelial cells

The endothelium plays a critical role in regulating leukocyte recruitment and migration during inflammation. Recent studies provide evidence that acetylcholine (ACh) and other cholinergic mediators block endothelial cells activation and leukocyte recruitment during inflammation. We thus postulated that the non-neuronal cholinergic system might modulate the recruitment of neutrophils during allergic pulmonary inflammation. In the present study, we examined the effects of cholinergic stimulation on the expression of neutrophil chemokines and adhesion molecules by endothelial cells stimulated by recombinant equine (re) IL-4. Using primary equine pulmonary artery endothelial cells culture and real-time RT-PCR method, we observed that ACh, nicotine, and muscarine inhibit the expression of E-selectin and vascular endothelial growth factor by endothelial cells stimulated by reIL-4. The expression of CXCL-8, a potent neutrophil chemotactic cytokine, remained unaffected however. These findings suggest that the cholinergic anti-inflammatory pathway may modulate pulmonary allergic inflammation and remodeling by the inhibition of selected adhesion molecules and growth factors.