{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:06:34Z","timestamp":1753880794176,"version":"3.41.2"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2320-B006-011"],"award-info":[{"award-number":["MOST 105-2320-B006-011"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2320-B006-011"],"award-info":[{"award-number":["MOST 106-2320-B006-011"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Group A\n            <jats:named-content content-type=\"genus-species\">Streptococcus<\/jats:named-content>\n            (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 an NADPH oxidase-dependent regulated process. In the present study, membrane translocation of NADPH oxidase subunit p47\n            <jats:sup>phox<\/jats:sup>\n            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 and NO, tumor necrosis factor alpha, and interleukin-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-3\u03b2 (GSK-3\u03b2) activation, and subsequent NF-\u03baB nuclear translocation, which were also markedly inhibited by treatment with DM and an NADPH oxidase inhibitor, diphenylene iodonium. These results suggest that DM attenuates GAS infection-induced overactive inflammation by inhibiting NADPH oxidase-mediated ROS production that leads to downregulation of the GSK-3\u03b2\/NF-\u03baB\/NO signaling pathway.\n          <\/jats:p>","DOI":"10.1128\/aac.02045-17","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T10:11:05Z","timestamp":1522145465000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Dextromethorphan Attenuates NADPH Oxidase-Regulated Glycogen Synthase Kinase 3\u03b2 and NF-\u03baB Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection"],"prefix":"10.1128","volume":"62","author":[{"given":"Chia-Ling","family":"Chen","sequence":"first","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao-Huei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nursing, I-Shou University, Kaohsiung, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Feng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Nursing, I-Shou University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Lin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Han","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Peng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiunn-Jong","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"},{"name":"Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Anderson","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"},{"name":"Departments of Microbiology &amp; Immunology and Pediatrics, and Canadian Center for Vaccinology, Dalhousie University, Halifax, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Jane","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Chuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"},{"name":"Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yee-Shin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"publisher","key":"e_1_3_3_2_2","DOI":"10.1128\/CMR.00101-13"},{"key":"e_1_3_3_3_2","first-page":"11","volume-title":"Streptococcus pyogenes: basic biology to clinical manifestations","author":"Stevens DL","year":"2016","unstructured":"Stevens DL, Bryant AE. 2016. 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