Dextromethorphan Attenuates NADPH Oxidase-regulated GSK-3 β and NF-κB Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection.

Dextromethorphan Attenuates NADPH Oxidase-regulated GSK-3β and NF-κB Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection. Antimicrob Agents Chemother. 2018 Mar 26;: Authors: Chen CL, Cheng MH, Kuo CF, Cheng YL, Li MH, Chang CP, Wu JJ, Anderson R, Wang S, Tsai PJ, Liu CC, Lin YS Abstract Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), an antitussive drug, has been demonstrated to efficiently reduce inflammatory responses thereby contributing to an increased survival rate of GAS-infected mice. However, the anti-inflammatory mechanisms underlying DM treatment in GAS infection remain unclear. DM is known to exert neuroprotective effects through a NADPH oxidase-dependent regulated process. In the present study, membrane translocation of NADPH oxidase subunit p47phox and subsequent reactive oxygen species (ROS) generation induced by GAS infection were significantly inhibited via DM treatment in RAW264.7 murine macrophage cells. Further determination of proinflammatory mediators revealed that DM effectively suppressed inducible nitric oxide synthase (iNOS) expression, NO, TNF-α and IL-6 generation in GAS-infected RAW264.7 cells as well as in air-pouch-infiltrating cells from GAS/DM-treated mice. GAS infection caused AKT dephosphorylation, glycogen synthase kinase-...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research