IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells.
Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the expression of CXCL-8, E-selectin, vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS), or potentiated the coeffects of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on CXCL-8. Supernatants collected from cultured endothelial cells stimulated with reIL-4 significantly promoted neutrophil migration in a dose-dependent manner. Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS. DXM and 1400W attenuated the mRNA expression of E-selectin and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS. Neither equine nor human recombinant IL-5 influenced the mRNA expression of CXCL-8, E-selectin, or VEGF. These findings suggest that Th2-type cytokines may contribute to pulmonary neutrophilia during allergic inflammation by the increased expression of neutrophil chemokines and adhesion molecules by endothelial cells. DXM and the iNOS inhibitors may decrease pulmonary neutrophilia due, in part, to a direct inhibition of some of these factors.
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1400W dihydrochloride 1400W DXM 1400W DXM nitric oxide Dexamethasone DXM nitric oxide CXCL-8 VEGF iNOS reIL-4 iNOS E-selectin VEGF iNOS E-selectin iNOS reIL-4 reTNF-alpha equine nor human recombinant IL-5 CXCL-8 E-selectin VEGF cytokines chemokines adhesion molecules iNOS equine (re) IL-4 reIL-5 cytokine reIL-4 ReIL-4 CXCL-8 E-selectin vascular endothelial growth factor VEGF inducible nitric oxide synthase iNOS tumor necrosis factor-alpha cytokines TNF-alpha CXCL-8 reIL-4 IL-4 CXCL-8 E-selectin VEGF inducible nitric oxide synthase