Inhibition of the MAP kinase ERK protects from lipopolysaccharide-induced lung injury

摘要: The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by inflammation associated with lung neutrophilia and elevated levels pro-inflammatory mediators in the bronchoalveolar lavage fluid or sputum patients. Recent findings revealed that mitogen-activated protein kinase (MAPK) signaling cascade involved inflammatory response injury. In present study we could elucidate role extracellular signal-related MAPK murine model LPS-induced acute injury using U0126, a specific inhibitor MEK1/2, upstream kinases ERK. Phosphorylation ERK was inhibited U0126 vivo as well vitro. freshly isolated human peripheral blood mononuclear cells dose-dependently blocked release IL-2 TNF-alpha. For studies mice were exposed to aerosolized LPS induce an mimicking some aspects COPD. This led recruitment neutrophils cytokines into lavage. Pretreatment significantly reduced diminished TNF-alpha chemotactic MIP-2 KC fluid. also decreased albumin BAL fluid, marker vascular leakage. Histological examination tissues inhibition efficiently attenuated responses. These data suggest plays important pharmacologic provides promising new therapeutic strategy for diseases particular