Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
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...
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PeerJ Inc.
2023-01-01
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| Online Access: | https://peerj.com/articles/14695.pdf |
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| author | Yasuhiro Kimura Masahiro Shinoda Masaharu Shinkai Takeshi Kaneko |
| author_facet | Yasuhiro Kimura Masahiro Shinoda Masaharu Shinkai Takeshi Kaneko |
| author_sort | Yasuhiro Kimura |
| collection | DOAJ |
| description | 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. MUC5AC, SPDEF, CLCA1, and ANO1 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 MUC5AC, CLCA1 and ANO1 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 CLCA1 and ANO1 mRNA and protein expression. However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin. |
| first_indexed | 2024-03-09T06:59:42Z |
| format | Article |
| id | doaj.art-05dc7e0fc828486c873cd93c9528e73a |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:59:42Z |
| publishDate | 2023-01-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-05dc7e0fc828486c873cd93c9528e73a2023-12-03T09:53:35ZengPeerJ Inc.PeerJ2167-83592023-01-0111e1469510.7717/peerj.14695Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cellsYasuhiro Kimura0Masahiro Shinoda1Masaharu Shinkai2Takeshi Kaneko3Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, JapanDepartment of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, JapanDepartment of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, JapanDepartment of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, JapanSolithromycin 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. MUC5AC, SPDEF, CLCA1, and ANO1 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 MUC5AC, CLCA1 and ANO1 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 CLCA1 and ANO1 mRNA and protein expression. However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin.https://peerj.com/articles/14695.pdfSolithromycinGoblet cellSAM pointed domain containing ETS transcription factorChloride channel accessory 1MucinMUC5AC |
| spellingShingle | Yasuhiro Kimura Masahiro Shinoda Masaharu Shinkai Takeshi Kaneko Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells PeerJ Solithromycin Goblet cell SAM pointed domain containing ETS transcription factor Chloride channel accessory 1 Mucin MUC5AC |
| title | Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells |
| title_full | Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells |
| title_fullStr | Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells |
| title_full_unstemmed | Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells |
| title_short | Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells |
| title_sort | solithromycin inhibits il 13 induced goblet cell hyperplasia and muc5ac clca1 and ano1 in human bronchial epithelial cells |
| topic | Solithromycin Goblet cell SAM pointed domain containing ETS transcription factor Chloride channel accessory 1 Mucin MUC5AC |
| url | https://peerj.com/articles/14695.pdf |
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