Never in Mitosis Gene A-Related Kinase Inhibition Alleviates Inflammation in an In Vivo Model of Acute Lung Injury.

Abstract

Chronic lung inflammation affects alveolar-capillary permeability and results in impaired gas exchange which may lead to edema, acute lung injury, and acute respiratory distress syndrome. The serine/threonine kinase NEK2, a member of the NIMA-related kinase family, regulates the cell cycle. This kinase was recently implicated in lung inflammation progression since it has been involved in barrier dysfunction and reactive oxygen species generation. This study investigated the effects of a selective NEK2 inhibitor, NCL 00017509, in a murine model of LPS-induced ALI. C57BL/6 male mice received an intratracheal injection of saline or LPS and were post-treated with NEK2 inhibitor or vehicle. Bronchoalveolar lavage fluid (BALF) was collected via tracheal catheterization, and western blot analysis was used to detect protein expression levels. Administration of the NEK2 inhibitor significantly reduced BALF protein concentration, indicating mitigation of lung edema. Moreover, NEK2 inhibition attenuated LPS-induced activation of the JAK/STAT, MAPK signaling, and reduced IL-1α, IL-1β, and IL-17A expression in lung tissues. Furthermore, NEK2 inhibition counteracted LPS-induced Grp94 and BiP suppression. Overall, it is suggested that NEK2 inhibition may alleviate complications related to vascular barrier dysfunction.