Work

CC16 alleviates PM2.5-induced lung epithelial cell injury and airway inflammation in asthmatic mice by inhibiting ferroptosis

Year: 2024

Type: article

Abstract: Exposure to PM2.5 represents a significant public health challenge, closely associated with the worsening of asthma, a condition that still lacks effective preventive measures. Club Cell 16 kDa protein (CC16), recognized for its anti-inflammatory and antioxidant properties, may serve a protective function in asthma exacerbated by PM2.5; however, the underlying mechanisms, particularly those related to ferroptosis, remain poorly understood. The impact of CC16 on inflammation and ferroptosis was assessed using a TC-1 lung epithelial cell model exposed to PM2.5, as well as an ovalbumin (OVA)-induced asthmatic mouse model also subjected to PM2.5 exposure. CC16 significantly modulated key regulators of ferroptosis (NRF2, GPX4, SLC7A11, HO-1) and attenuated pro-inflammatory cytokines (IL-13, IL-5, IL-6, IL-1β, IL-17A) in PM2.5-exposed lung epithelial cells. Furthermore, it enhanced pulmonary function while reducing airway inflammation and mucus secretion and inhibited ferroptosis in PM2.5-induced asthmatic mice. CC16 demonstrates promise as a therapeutic agent for PM2.5-induced asthma by modulating ferroptosis and alleviating airway inflammation, thereby providing a novel strategy for asthma management. CC16 significantly modulates the expression of NRF2 and its downstream effectors, including GPX4, SLC7A11, and HO-1, in OVA and PM2.5-induced asthmatic mice. It reduces the production of pro-inflammatory cytokines and oxidative stress markers while inhibiting ferroptosis, thereby alleviating asthma symptoms • CC16 alleviates PM2.5-induced cell injury in vitro and airway inflammation in vivo is proposed. • The mechanism relies on its inhibitory effect on ferroptosis by modulating Nrf2 and the downstream molecules. • CC16 can promote the proliferation of mouse lung epithelial cells, and has no damage to normal mouse lung tissue. • It may be a promising candidate for the prevention and treatment of PM2.5-induced acute exacerbation of asthma.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2024.117417