Effect of retinoid X receptor partial agonist on airway inflammation and hyperresponsiveness

Rationale: Retinoid X receptors (RXRs) are members of nuclear receptor (NR) superfamily that mediates signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play a key role as heterodimeric partners, e.g., Retinoid acid receptors (RARs), vitamin D receptors (VDRs), and peroxisome proliferator-activated receptors (PPARs). Recently, NR family is reported to associate with allergic diseases, nonetheless the role of RXRs in allergen-induced airway responses is not well defined. Methods: We investigated the effect of novel partial RXR agonist (Net-4IB) on the development of allergic airway inflammation and airway hypperresponsiveness (AHR) in asthma mice model. Balb/c mice were sensitized (days 0 and 14) and challenged (days 28-30) with ovalbumin (OVA), and airway inflammation and airway responses were monitored 48 hours after the last OVA-challenge. Net-4IB was administered orally on days 25 to 32. Result: Oral administration with Net-4IB significantly suppressed AHR, inflammatory cells accumulation in the airways, and attenuated the levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid and the numbers of PAS positive cells in the lung tissue. Conclusion: These date suggest that Net-4IB may play an important role in the development of allergic airway inflammation and airway hyperresponsiveness in a murine model of asthma.