In the present study, we investigated whether the activation of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (Erk1/2) are involved in the induction of MMP-9 in lipopolysaccharide (LPS)-stimulated primary astrocytes. The expression of MMP-9 but not MMP-2 was increased by LPS. LPS treatment induced activation of Erk1/2 within 30 min, which was dose-dependently inhibited by PD98059, a specific inhibitor of the Erk kinase (MEK). In this condition, PD98059 blocked the increase in MMP-9 protein and mRNA level as well as gelatin-digesting activity. Inhibition of PKC activity blocked the LPS-induced activation of Erk1/2 as well as MMP-9 expression. In addition, activation of PKC by phorbol myristoyl acetate (PMA) activated Erk1/2 with concomitant increase in MMP-9 production. Moreover, treatment of PD98059 dose-dependently decreased the PMA-induced MMP-9 expression. The results from the present study suggest that induction of MMP-9 by LPS in rat primary astrocytes is mediated, at least in part, by the sequential activation of PKC and Erk1/2. The Erk1/2-mediated MMP-9 induction may provide insights into the regulation of MMP-9 production in CNS, which may occur in vivo in pathological situations such as CNS inflammation.

The root of Platycodon grandiflorum has been widely used for the treatment of various chronic inflammatory diseases including airway disease in oriental medicine. The root extract of the plant has been known to be effective in the expectoration of sputum or mucus, thereby improving airway respiratory function and preventing secondary airway inflammation. In this study, we investigated the effect of platycodin D and D3, the saponin components that are anti-inflammatory components in Platycodon grandiflorum. Platycodin D and D3 increased mucin release from rat and hamster tracheal surface epithelial cell culture and also from intact rat trachea upon nebulization. The effect of platycodin D3 was stronger than that of ATP, a potent mucin secretagogue and also of ambroxole, a mucolytic drug. The results from the present study suggest that platycodin D and D3 are useful as expectorant agents in the treatment of various airway diseases.

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By analyzing a large panel of elections in 55 countries, we show that political uncertainty surrounding elections can affect asymmetric cost responses to activity changes (i.e., cost stickiness). In comparison to non‐election years, we find that the asymmetry in cost behaviors is stronger during election years in regressions that control for other firm‐level and country‐level determinants. In another series of tests, we report strong, robust evidence supporting the predictions that the importance of political uncertainty to cost stickiness is concentrated in countries with sound political and legal institutions. Collectively, the results imply that managers retain slack resources when political uncertainty is high but to be resolved soon.

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