IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells.
Abstract: 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.
Publication Date: 2007-05-15 PubMed ID: 17494951DOI: 10.1152/ajplung.00294.2006Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigated the role of T helper 2 (Th2) type cytokines in the movement of neutrophils into the lung tissue, using equine pulmonary artery endothelial cells. It found that the presence of such cytokines may increase neutrophil chemokines and adhesion molecules, thereby potentially contributing to inflammation during an allergic response. Dexamethasone (DXM) and inducible nitric oxide synthase (iNOS) inhibitors can help reduce this response by directly inhibiting some of these factors.
Research background and motivation
- The research aimed to get a deeper understanding of how Th2-type cytokines contribute to the process of bringing neutrophils into the lung tissue, a process that is not well-known as of yet.
- The researchers hypothesized that these cytokines could increase the expression of molecules that aid the movement and chemotaxis of neutrophils, thereby contributing to allergic inflammations.
Research method
- Endothelial cells from equine pulmonary arteries were cultured with recombinant equine IL-4 and IL-5.
- The mRNA expression of molecules linked to the chemotaxis and migration of neutrophils was investigated using real-time RT-PCR.
- A chemotaxis chamber was used to study how IL-4-induced stimulation of endothelial cells influenced neutrophil movement.
Findings
- IL-4 increased the expression of CXCL-8, E-selectin, VEGF, and iNOS, or enhanced the effects of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on CXCL-8.
- Supernatants collected from cells stimulated with IL-4 promoted neutrophil migration in a dose-dependent fashion.
- The use of dexamethasone (DXM) reduced IL-4 induced expression of CXCL-8, VEGF, and iNOS, while 1400W, an inhibitor of iNOS, reduced the expression of E-selectin, VEGF, and iNOS.
- Both DXM and 1400W subdued the mRNA expression of E-selectin and iNOS induced by the co-stimulation of IL-4, TNF-alpha, and LPS.
- Neither recombinant equine nor human IL-5 affected the mRNA expression of CXCL-8, E-selectin, or VEGF.
Implications
- These findings suggest that Th2-type cytokines may cause pulmonary neutrophilia during allergic inflammation by the increased expression of neutrophil chemokines and adhesion molecules by endothelial cells.
- DXM and iNOS inhibitors may help reduce pulmonary neutrophilia due to their ability to inhibit some of these factors.
Cite This Article
APA
Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP.
(2007).
IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells.
Am J Physiol Lung Cell Mol Physiol, 292(5), L1147-L1154.
https://doi.org/10.1152/ajplung.00294.2006 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
MeSH Terms
- Animals
- Cell Culture Techniques
- E-Selectin / genetics
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / physiology
- Factor VIII / analysis
- Horses
- Interleukin-4 / pharmacology
- Interleukin-8 / genetics
- Nitric Oxide Synthase Type II / genetics
- Pulmonary Artery / drug effects
- Pulmonary Artery / physiology
- RNA, Messenger / genetics
- Reverse Transcriptase Polymerase Chain Reaction
- Vascular Endothelial Growth Factor A / genetics
Citations
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