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

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.