Interleukin-17A and vascular remodeling in severe asthma; lack of evidence for a direct role

Abstract

Background

Bronchial vascular remodeling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodeling is uncertain.

Objective

To assess vascular remodeling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis.

Methods

Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A⁺ cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation.

Results

Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A⁺ cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC.

Conclusions & Clinical Relevance

Our results shed light on the role of IL-17A in vascular remodeling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets.

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