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

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. [Display omitted] •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.