Short-term cigarette smoke exposure aggravates oxidative stress and airway inflammation induced by lipopolysaccharides.

AIM: This study discloses the early synergistic effects of short-term cigarette smoke (CS) exposure combined with lipopolysaccharide (LPS) on pulmonary inflammation and tissue stress. METHOD: Six- to eight-week-old BALB/c mice were divided into CS-exposed groups (9 cigarettes per day for 4 days) and sham-exposed control groups. On the fourth day, intratracheal instillation of LPS or saline was administered to both groups. The study examined several indicators, including changes in body weight, bronchoalveolar lavage fluid (BALF) cell counts, mRNA expression of inflammatory factors and oxidative stress markers, lung histopathology, and airway remodeling markers. RESULT: The results showed that short-term CS exposure alone did not induce significant oxidative stress or inflammation. However, short-term CS exposure exacerbated LPS-induced pulmonary inflammation, as evidenced by increased expression of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α. It also intensified oxidative stress, as indicated by upregulation of NADPH oxidase 2 (NOX2) and heme oxygenase-1 (HO-1). Additionally, activation of early airway remodeling-associated signaling was observed, with elevated expression of collagen I/III, alpha-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1). These effects occurred through activation of NF-κB-mediated inflammatory pathways, increased macrophage-derived reactive oxygen species (ROS) production, and reduced antioxidant defenses. Notably, short-term CS exposure did not significantly affect the number of immune cells in BALF after LPS stimulation. CONCLUSION: These results indicate that short-term CS exposure can "sensitize" the lungs-that is, increase their sensitivity-to acute lung injury upon subsequent bacterial stimulation. These findings suggest that even brief CS exposure may increase sensitivity to infection-associated acute lung injury in passive or intermittent smokers.