Chalcone 4 treatment decreases the migration of dendritic cells into jugular nodose ganglia in an OVA-induced mouse model of allergic asthma

Background:

The CXC-motif receptor 4 (CXCR4) and its ligand, the chemokine CXCL12 have been shown to play a pivotal role in the progress of bronchial asthma.

Objective:

The objective was to study the effect of the CXCL12 neutraligand chalcone 4 on the allergic airway inflammation and to analyze the migration of CXCR4⁺ dendritic cells in an OVA-mouse model for allergic airway inflammation.

Methods:

A 21-days BALBc-OVA-mouse model was used to induce allergic airway inflammation. One group received 300nmol/kg body weight chalcone 4 on 4 days starting five days before final analysis. BALF cell count and immunohistochemistry of dendritic cell migration in JNC and expression of neuropeptides CGRP and substance P were performed. Th2-cytokinins were evaluated in the BALF with ELISA.

Results:

Allergic airway inflammation in the OVA-treated and OVA-chalc4-treated groups was demonstrated by a significantly increased influx of inflammatory cells in the BALF. Chalcone 4 caused a significant decrease of the dendritic cell-migration into jugular nodose ganglia of approximately 20% in OVA-Chalc4 mice compared to OVA-solvent mice. It did not affect the expression of CGRP and substance P significantly. Furthermore, IL-5 and IL-13, but not of IL-4, were found to be significantly decreased in chalcone 4-treated mice.

Conclusion:

The CXCL12 neutraligand chalcone 4 affected the migration of dendritic cells into the airways and airway ganglia, reduced the antigen presentation and therewith decreased the allergic airway inflammation. Inhibition of CXCR 4 through neutralizing its ligand with chalcone 4 may have valuable effects in the pharmacological therapy of allergic diseases such as allergic bronchial asthma.