Effects of a CB2 Receptor Inverse Agonist on Airway Remodeling and TH1/TH2 Imbalance in Rats with Bronchial Asthma via the TLR4/NF-κB Signaling Pathway

Abstract

Bronchial asthma (BA) has a complex pathogenesis involving immune imbalance and airway remodeling (AR). Cannabinoid receptor 2 (CB2) plays a role in inflammation regulation, so this study explored the therapeutic potential of a CB2 inverse agonist on BA rats’ AR and Th1/Th2 imbalance, and its mechanism via Toll-like receptor 4/nuclear factor kappa B(TLR4/NF-κB) pathway. Twenty-seven male SD rats (180-220 g) were divided into control (CG), model (MG), and intervention (IG) groups (n=9 each). MG/IG were BA-modeled by ovalbumin (OVA) sensitization (days 1/8: 100 μg OVA +1 mg aluminum hydroxide gel, i.p.) and 1% OVA aerosol challenge (day 15, 3×/week, 8 weeks). IG received CB2 inverse agonist (5 mg/kg, i.p., 3×/week, 4 weeks); CG/MG got saline. TH1/TH2 cytokines, subsets, AR parameters, and lung TLR4/NF-κB-related molecules were detected. Compared with CG, MG had TH1/TH2 imbalance, higher AR indices, upregulated TLR4/NF-κB, shorter asthma latency, and longer attack duration. vs. MG, IG reversed TH1/TH2 imbalance, reduced TLR4/NF-κB-related protein/mRNA (except elevated NFKBIA). CB2 inverse agonist has BA prevention/treatment potential by regulating Th1/Th2 balance, inhibiting AR, and acting on the TLR4/NF-κB pathway.