{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:14:25Z","timestamp":1774412065107,"version":"3.50.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Yokohama City University Research Fund"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Activation of the interleukin-13 (IL-13) receptor leads to signal transducer and activator of transcription 6 (STAT6) activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF) and chloride channel accessory 1 (CLCA1), increasing secretion of the gel-forming mucin MUC5AC. Activation of the epidermal growth factor receptor (EGFR) also leads to MUC5AC production via extracellular signal-regulated kinase (ERK1\/2). We examined the effect of clarithromycin IL-13 signaling leading to production. Normal human bronchial epithelial (NHBE) cells were grown for 14 days at an air-liquid interface (ALI) with IL-13 and\/or clarithromycin. Histochemical analysis was performed using hematoxylin and eosin (HE) staining and MUC5AC immunostaining. MUC5AC, SPDEF, and CLCA1 mRNA expression were evaluated by real-time PCR. Western analysis was used to assess phosphorylation of STAT6 and ERK1\/2. Clarithromycin decreased IL-13-induced goblet cell hyperplasia and MUC5AC mRNA expression in a dose-dependent manner. Clarithromycin decreased IL-13-stimulated SPDEF and CLCA1 mRNA expression in a dose-dependent manner, and at 32 \u03bcg\/ml CLCA1 was profoundly decreased (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). Although clarithromycin had no effect on STAT6 phosphorylation induced by IL-13, it decreased constitutive phosphorylation of ERK1\/2 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05).\n          <\/jats:p>","DOI":"10.1128\/aac.01327-16","type":"journal-article","created":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T02:18:28Z","timestamp":1471918708000},"page":"6585-6590","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Clarithromycin Suppresses Chloride Channel Accessory 1 and Inhibits Interleukin-13-Induced Goblet Cell Hyperplasia in Human Bronchial Epithelial Cells"],"prefix":"10.1128","volume":"60","author":[{"given":"Akimichi","family":"Nagashima","sequence":"first","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Shinkai","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Shinoda","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadasuke","family":"Shimokawaji","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Mishina","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sato","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Toda","sequence":"additional","affiliation":[{"name":"Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Inayama","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce K.","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, 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SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. 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