Choline chloride attenuates the allergic airway disease by inhibiting the lysophosphatidylcholine induced response in mouse model

Aims

Allergic airway disease manifestation is induced by lysophosphatidylcholine (LPC) through CD1d-restricted Natural killer T (NKT) cells. Choline chloride (ChCl) and LPC both have the “choline” moiety in their structure and this may interplay the effect in allergic airway disease pathway.

Main methods

To test the hypothesis, mice were sensitized with cockroach extract (CE); challenged with CE or exposed to LPC and were given ChCl 1hr later.

Key findings

A significant increase in Airway hyperresponsiveness (AHR), total and differential cell count, Th2 cytokines, 8-isoprostanes level in bronchoalveolar lavage fluid (BALF) and inflammation score based on lung histology were observed on challenge with CE or exposure to LPC (p ​< ​0.05) indicating LPC induced airway disease manifestation in mice. These parameters were reduced significantly after administering mice with ChCl (p ​< ​0.05). The inflammatory parameters were significantly increased in LPC exposed mice, not sensitized with CE, which were significantly decreased when mice were administered with ChCl demonstrating its role in the inhibition of LPC induced allergic airway disease manifestation. Docking of CD1d with LPC and ChCl indicated the competitive inhibition of LPC induced effect by ChCl. This was validated in vivo in the form of decreased CD1d-restricted NKT cells in BALF and lung of the immunized mice on ChCl administration. There was no effect of ChCl administration on CD1d expression in BALF and lung cells.

Significance

This study shows that ChCl attenuates the allergic response by inhibiting the LPC induced- NKT cell mediated AHR, inflammation and oxidative stress by competitive inhibition to LPC in binding to CD1d.