RKIP suppresses influenza A virus-induced airway inflammatory response via the ERK/MAPK pathway

Abstract Objective RKIP has been demonstrated as an inflammatory inhibiting mediator and involved in many diseases. However, the potential mechanism of RKIP on the inflammatory response induced by IAV was unclear. Methods The expression of RKIP and the change of inflammatory response were detected in BEAS-2B, DHBE and pNHBE cells infected by IAV. Locostatin was co-cultured with cells to downregulate the expression of RKIP. RKIP was overexpressed by transfecting lentivirus. And a small molecule inhibitor, SCH772984, specifically inhibited the activation of the ERK/MAPK pathway. C57BL/6 mice were also infected with IAV to further confirm our hypothesis in vivo. Results The expression of RKIP decreased inflammatory response was triggered by IAV infection in airway epithelial cells characterized by increased inflammatory cytokines and cell cycle arrest. Meanwhile, the ERK/MAPK pathway was activated by IAV infection. The results also showed that the down-expression of RKIP aggravated the airway inflammatory response. Conversely, overexpression of RKIP effectively alleviated the airway inflammatory response induced by IAV. Conclusions This study demonstrated RKIP played a protect role in airway epithelial cells against the inflammation via the ERK/MAPK pathway. Collectively, our findings suggested that RKIP negatively regulates airway inflammation and could be a promising therapeutic strategy for airway inflammatory related diseases induced by IAV.