Lactobacillus rhamnosus regulates airway epithelial cell senescence through the ADCK5/PI3K/AKT signaling axis and alleviates airway inflammation in asthma

Lactobacillus rhamnosus (LGG) can alleviate ovalbumin (OVA)-induced asthma, but whether its mechanism of action involves cell senescence is unknown. OVA was used to establish a mouse model of asthma. LGG was administered by oral gavage, and a lentivirus carrying aarF domain containing kinase 5 (ADCK5) was injected intravenously to overexpress ADCK5. The Penh value of the airway response in the mice was measured by a whole-body plethysmography system. Airway epithelial cell senescence was assessed using an SA-β-gal kit, immunofluorescence, and Western blotting. DCFH-DA, ELISA, a JC-1 fluorescent probe, a transmission electron microscope, immunofluorescence, and Kwik-Diff staining were used to evaluate oxidative stress and the inflammatory response in the lung tissue of the mice. Finally, the expression of the ADCK5/PI3K/AKT axis was detected by Western blotting. LGG improved AHR levels in OVA-induced asthmatic mice; alleviated inflammatory infiltration, tube wall thickening, goblet cell hyperplasia, and collagen deposition in lung tissues; and reduced the number of SA-β-gal-positive cells and P21 and P16 expression. LGG can reduce ROS and γH2AX levels, increase MMP levels, improve mitochondrial structural damage, and reduce the levels of inflammatory factors in BALF and the IgE concentration in serum. LGG also reduced ADCK5, p-PI3K, and p-AKT levels. ADCK5 overexpression increased the number of SA-β-gal-positive cells and the P21, P16, p-PI3K, p-AKT, ROS, and γH2AX levels; decreased the MMP; and increased the inflammatory factor and IgE concentrations. LGG may reduce oxidative stress and the inflammatory response potentially through inhibiting the ADCK5/PI3K/AKT axis, improving airway epithelial cell senescence, and thus alleviating asthma.