p21 facilitates chronic lung inflammation via epithelial and endothelial cells
Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, Valery Krizhanovsky
Abstract
) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to chronic bronchitis and accumulation of senescent cells. p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and endothelial cells, but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure. Our results implicate p21 as a critical regulator of chronic bronchitis and a driver of chronic airway inflammation and lung destruction.