{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T22:48:41Z","timestamp":1773182921363,"version":"3.50.1"},"reference-count":40,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A Grant-in-Aid for Scientific Research (KAKENHI) for Masaharu Shinkai","award":["15K09183"],"award-info":[{"award-number":["15K09183"]}]},{"name":"Yokohama City University Research Fund for Masaharu Shinkai and Takeshi Kaneko"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Solithromycin is a novel fluoroketolide antibiotic belonging to the class of macrolide antibiotics. Activation of the interleukin (IL)-13 receptor leads to STAT6 activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF), chloride channel accessory 1 (CLCA1), and anoctamin-1 (ANO1), all of which are associated with the induction of MUC5AC. We examined the effects of solithromycin on mucin production led by IL-13 signaling. Normal human bronchial epithelial cells were grown at the air-liquid interface with IL-13 with\/without solithromycin for 14 days. Histochemical analysis was performed using hematoxylin and eosin staining and MUC5AC immunostaining. <jats:italic>MUC5AC<\/jats:italic>, <jats:italic>SPDEF<\/jats:italic>, <jats:italic>CLCA1<\/jats:italic>, and <jats:italic>ANO1<\/jats:italic> mRNA expressions were examined using real-time polymerase chain reaction. Western blot analysis was performed to assess CLCA1 and ANO1 proteins, and phosphorylation of STAT6 and ERK. Solithromycin attenuated IL-13 induction of goblet cell hyperplasia and <jats:italic>MUC5AC<\/jats:italic>, <jats:italic>CLCA1<\/jats:italic> and <jats:italic>ANO1<\/jats:italic> mRNA and protein expression induced by IL-13, but had no effect on the phosphorylation of STAT6 and ERK. Our results indicate that solithromycin could attenuate goblet cell hyperplasia and MUC5AC induced by IL-13 through inhibition of <jats:italic>CLCA1<\/jats:italic> and <jats:italic>ANO1<\/jats:italic> mRNA and protein expression. However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin.<\/jats:p>","DOI":"10.7717\/peerj.14695","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T08:20:38Z","timestamp":1673943638000},"page":"e14695","source":"Crossref","is-referenced-by-count":8,"title":["Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells"],"prefix":"10.7717","volume":"11","author":[{"given":"Yasuhiro","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama,  Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Shinoda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Shinkai","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama,  Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"10.7717\/peerj.14695\/ref-1","doi-asserted-by":"publisher","first-page":"4555","DOI":"10.1172\/JCI64896","article-title":"IL-13-induced airway mucus production is attenuated by MAPK13 inhibition","volume":"122","author":"Alevy","year":"2012","journal-title":"The Journal of Clinical 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