MKP1 regulates the induction of inflammatory response by pneumococcal pneumolysin in human epithelial cells

Abstract

The expression of proinflammatory cytokines represents an important host innate response during infections. The reduction of cytokine expression thus mediates impaired host defenses. We previously reported that pneumococcal pneumolysin is less potent in inducing inflammatory responses in human epithelial cells at the early stage of treatment. How this might occur in response to pneumolysin is still not clearly understood. Here, we show the expression of tumor necrosis factor-alpha (TNF-alpha) was reduced by MAPK phosphatase 1 (MKP1), expression of which was significantly increased in response to pneumolysin at the early stage of treatment. TNF-alpha expression was mediated in a time-dependent manner by p38 mitogen-activated protein kinase, activation of which is under the control of MKP1. Thus, this study reveals novel roles of pneumolysin in mediating MKP1 expression for the regulation of proinflammatory cytokine expression in a time-dependent manner.