Interleukin-17 antagonist attenuates lung inflammation through inhibition of the ERK1/2 and NF-κB pathway in LPS-induced acute lung injury

Abstract

Interleukin (IL)-17 has been implicated in a variety of inflammatory lung diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). Therefore, the aim of the present study was to confirm whether the increase in IL-17 expression following ALI enhances expression of inflammatory cytokines/chemokines through activation of the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-κB signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury; which, in turn, can be blocked by an IL-17 antagonist. The authors indicated that levels of IL-17 mRNA and protein were elevated in the bronchoalveolar lavage fluid (BALF) and lung tissues of ALI rats, and upregulation of IL-17 resulted in the enhanced severity of lung injury. Moreover, treatment with an IL-17 neutralizing antibody significantly inhibited the increases of parameters of ALI in rats, as evidenced by decreased histologic scores, BALF exudate volume, protein leakage and wet-to-dry weight ratio. In addition, management of IL-17 may markedly mitigate LPS-induced pulmonary inflammation, as reflected by the reduced levels of a multitude of proinflammatory cytokines in BALF. Of note, blockade of IL-17 effectively inhibited LPS-induced expression and activation of p-ERK1/2 and nuclear factor (NF)-κB p65 in lung tissues, and suppressed nuclear translocation of NF-κB p65. These results indicated that IL-17 serves an important role in LPS-induced ALI via stimulation of the ERK1/2 and NF-κB signaling pathway, and serves as a potential therapeutic target for treating LPS-induced ALI.