CycloZ Suppresses TLR4-Driven Inflammation to Reduce Asthma-Like Responses in HDM-Exposed Mouse Models

Abstract

Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, and narrowing, with a risk of life-threatening attacks. Most current treatments primarily consist of inhalable steroids, which are not without adverse effects. Recently, there has been growing interest in alternative approaches to asthma management. In this study, we investigated the anti-asthmatic effects of the non-steroidal compound CycloZ using acute and chronic mouse models of asthma. Allergic reactions were induced with house dust mite (HDM) extract, and CycloZ or fluticasone propionate (FP) was administered orally or intranasally, respectively. CycloZ significantly ameliorated the HDM-induced robust expression of Th2 cytokines in both models. CycloZ also decreased immune cell infiltration into the lungs and reduced IL-4 and IL-13 cytokine levels in bronchoalveolar lavage fluid (BALF). Moreover, CycloZ greatly attenuated the activation of the TLR-4 pathway, which is involved in HDM recognition and signaling. The beneficial effects of CycloZ were comparable to or even superior to the current steroid treatment, FP, suggesting that CycloZ could be a promising new option for asthma therapy.

Keywords

• asthma
• HDM
• inflammation
• TLR4